CAMP-dependent protein kinase - AbsoluteAstronomy.com

Cell biology

Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

, Protein kinase A (PKA) refers to a family of enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase . Protein kinase A has several functions in the cell, including regulation of glycogen

Glycogen

Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

, sugar

Sugar

Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...

, and lipid

Lipid

Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

.

It should neither be confused with AMP-activated protein kinase

AMP-activated protein kinase

5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis. It consists of three proteins that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of...

- which, although being of similar nature, may have opposite effects - nor with cyclin-dependent kinases (Cdks).

Activation

Each PKA is a holoenzyme that consists of two regulatory and two catalytic subunit

Protein subunit

In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

s. Under low levels of cAMP, the holoenzyme remains intact and is catalytically inactive. When the concentration of cAMP rises (e.g., activation of adenylate cyclase

Adenylate cyclase

Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

s by G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

s coupled to G_s

Gs alpha subunit

The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...

, inhibition of phosphodiesterase

Phosphodiesterase

A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...

s that degrade cAMP), cAMP binds to the two binding site

Binding site

In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...

s on the regulatory subunits, which leads to the release of the catalytic subunits.

Catalysis

The free catalytic subunits can then catalyse the transfer of ATP terminal phosphates to protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

substrate

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

s at serine

Serine

Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

, or threonine

Threonine

Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

residues

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

. This phosphorylation

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

usually results in a change in activity of the substrate. Since PKAs are present in a variety of cells and act on different substrates, PKA and cAMP regulation are involved in many different pathways.

The mechanisms of further effects may be divided into direct protein phosphorylation and protein synthesis:

In direct protein phosphorylation, PKA directly either increases or decreases the activity of a protein.
In protein synthesis, PKA first directly activates CREB
CREB
CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....

, which binds the cAMP response element, altering the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

and therefore the synthesis of the protein. In general, this mechanism takes more time (hours to days).

Inactivation

Thus, PKA is controlled by cAMP

Cyclic adenosine monophosphate

Cyclic adenosine monophosphate is a second messenger important in many biological processes...

. Also, the catalytic subunit itself can be down-regulated by phosphorylation.

Downregulation of protein kinase A occurs by a feedback mechanism: One of the substrates that are activated by the kinase is a phosphodiesterase

Phosphodiesterase

, which quickly converts cAMP to AMP, thus reducing the amount of cAMP that can activate protein kinase A.

Anchorage

The 2 regulatory subunits of protein kinase A are important for localizing the kinase inside the cell. With the aid of A-kinase anchor protein (AKAP), AKAP binds both to the regulatory subunits and to either a component of cytoskeleton structure or a membrane of an organelle, anchoring the enzyme complex to a particular subcellular compartment.

The catalytic function of protein kinase A would sometimes couple with the AKAP, binding PKA with phosphodiesterase to form a complex that functions as a signal module. For example, an AKAP locating near the nucleus of a heart muscle cell would bind to both PKA and phosphodiesterase that hydrolyzes cAMP. As phosphodiesterase contributes to the steady low concentration of cAMP in unstimulated cells, as the cell is stimulated, PKA is then responsible for the activation of phosphodiesterase (adjacent to PKA) in order to lower the concentration of cAMP. In this condition, as PKA and phosphodiesterase have formed a complex, the proximity increases the efficiency of PKA's activity.

Function

PKA phosphorylates other proteins, altering their function. As protein expression varies from cell type to cell type, the proteins that are available for phosphorylation will depend upon the cell in which PKA is present. Thus, the effects of PKA activation vary with cell type

Cell type

A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...

Overview table

Cell type Cell type A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...	Organ/system	Stimulators ligands --> G_s Gs alpha subunit The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:... -GPCR G protein-coupled receptor G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal... s or PDE inhibitors Phosphodiesterase inhibitor A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...	Inhibitors ligands --> G_i Gi alpha subunit Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors... -GPCR G protein-coupled receptor G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal... s or PDE Phosphodiesterase A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below... stimulators	Effects
adipocyte Adipocyte However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...		epinephrine Epinephrine Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines... --> β-adrenergic receptor glucagon Glucagon Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is... --> Glucagon receptor Glucagon receptor The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...		enhance lipolysis Lipolysis Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver... stimulate lipase Lipase A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
myocyte Myocyte A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell.... (skeletal muscle Skeletal muscle Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle... )	muscular system Muscular system The muscular system is the anatomical system of a species that allows it to move. The muscular system in vertebrates is controlled through the nervous system, although some muscles can be completely autonomous.- Muscles :...	epinephrine Epinephrine Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines... --> β-adrenergic receptor		produce glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... stimulate glycogenolysis Glycogenolysis Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate... phosphorylate glycogen phosphorylase Glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond... via phosphorylase kinase Phosphorylase kinase Phosphorylase kinase is a serine/threonine-specific protein kinase which activates glycogen phosphorylase to release glucose-1-phosphate from glycogen... (activating it) phosphorylate Acetyl-CoA carboxylase Acetyl-CoA carboxylase Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase... (inhibiting it) inhibit glycogenesis Glycogenesis Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels, for example after a... phosphorylate glycogen synthase Glycogen synthase Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers.... (inhibiting it) stimulate glycolysis Glycolysis Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+... phosphorylate phosphofructokinase 2 Phosphofructokinase 2 Phosphofructokinase 2 or fructose biphosphatase 2 , is an enzyme responsible for regulating the rates of glycolysis and gluconeogenesis in the human body. It is a homodimer of 55 kDa subunits arranged in a head-to-head fashion, with each polypeptide chain consisting of independent kinase and... (stimulating it, cardiomyocytes only)
myocyte Myocyte A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell.... (cardiac muscle Cardiac muscle Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle... )	muscular system Muscular system The muscular system is the anatomical system of a species that allows it to move. The muscular system in vertebrates is controlled through the nervous system, although some muscles can be completely autonomous.- Muscles :...	norepinephrine Norepinephrine Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter... --> β-adrenergic receptor		sequester Ca²⁺ in sarcoplasmic reticulum phosphorylates phospholamban Phospholamban Phospholamban, also known as PLN, is a protein that in humans is encoded by the PLN gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells.- Function :...
hepatocyte Hepatocyte A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...	liver Liver The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...	epinephrine Epinephrine Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines... --> β-adrenergic receptor glucagon Glucagon Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is... --> Glucagon receptor Glucagon receptor The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...		produce glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... stimulate glycogenolysis Glycogenolysis Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate... phosphorylate glycogen phosphorylase Glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond... (activating it) phosphorylate Acetyl-CoA carboxylase Acetyl-CoA carboxylase Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase... (inhibiting it) inhibit glycogenesis Glycogenesis Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels, for example after a... phosphorylate glycogen synthase Glycogen synthase Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers.... (inhibiting it) stimulate gluconeogenesis Gluconeogenesis Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids.... phosphorylate fructose 2,6-bisphosphatase (stimulating it) inhibit glycolysis Glycolysis Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+... phosphorylate phosphofructokinase -2 phosphatase (activating it) phosphorylate pyruvate kinase Pyruvate kinase Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:... (inhibiting it)
neuron Neuron A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous... s in nucleus accumbens Nucleus accumbens The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...	nervous system Nervous system The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...	dopamine Dopamine Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their... --> dopamine receptor Dopamine receptor Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....		Activate reward system Reward system In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
principal cells in kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	Vasopressin Vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's... --> V2 receptor Arginine vasopressin receptor 2 Arginine vasopressin receptor 2 is a protein that acts as receptor for arginine vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors... theophylline Theophylline Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it... (PDE inhibitor Phosphodiesterase inhibitor A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE... )		exocytosis Exocytosis Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane... of aquaporin 2 Aquaporin 2 AQP2 is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell.-Regulation:It is the only aquaporin regulated by vasopressin.... to apical membrane. synthesis of aquaporin 2 phosphorylation of aquaporin 2 (stimulating it)
myocyte Myocyte A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell.... (smooth muscle Smooth muscle Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by... )	muscular system Muscular system The muscular system is the anatomical system of a species that allows it to move. The muscular system in vertebrates is controlled through the nervous system, although some muscles can be completely autonomous.- Muscles :...	β2 adrenergic agonists --> β-2 adrenergic receptor Beta-2 adrenergic receptor The beta-2 adrenergic receptor , also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene encoding it.-Gene:The gene is intronless... histamine Histamine Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by... --> Histamine H2 receptor prostacyclin Prostacyclin Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:... --> prostacyclin receptor Prostacyclin receptor Prostacyclin receptor is a receptor for prostacyclin.-Transduction:When binding a prostacyclin-molecule, the receptor changes conformation and activates Gs, with its activation of cAMP and increase in protein kinase A activity.-In vasodilation:In vasodilation, the PKA activity causes... Prostaglandin D₂ Prostaglandin D2 Prostaglandin D2 is a prostaglandin that binds to the receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, basophils. In mammalian organs, large amounts of PGD2 are found in the brain, in mast cells and found nowhere else... --> PGD₂ receptor Prostaglandin D2 receptor Prostaglandin D2 receptor is a G-protein coupled receptor, encoded by the PTGDR gene, for prostaglandin D2.-Mechanism:DP1 is a G-protein-coupled receptor... Prostaglandin E₂ --> PGE₂ receptor Prostaglandin E2 receptor Prostaglandin E2 receptor , also known as EP2, is a prostaglandin receptor for prostaglandin E2. It is encoded by the human gene PTGER2.It may be associated with aspirin-induced asthma.-Mechanism:... VIP Vasoactive intestinal peptide Vasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain... --> VIP receptor Vasoactive intestinal peptide receptor There are two known receptors for the vasoactive intestinal peptide termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide to some degree... L-Arginine Arginine Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during... --> imidazoline Imidazoline receptor Imidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is... and α-2 receptor Alpha-2 adrenergic receptor The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well... ? (G_i Gi alpha subunit Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors... -coupled)	muscarinic agonists, e.g. acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> muscarinic receptor M₂ Muscarinic acetylcholine receptor M2 The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.-Heart:... NPY Neuropeptide Y Neuropeptide Y is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system."NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy." The main effect is increased food... --> NPY receptor	Vasodilation Vasodilation Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
Thick ascending limb cell	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	Vasopressin Vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's... --> V2 receptor Arginine vasopressin receptor 2 Arginine vasopressin receptor 2 is a protein that acts as receptor for arginine vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors...		stimulate Na-K-2Cl symporter Na-K-2Cl symporter The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important... (perhaps only minor effect)
Cortical collecting tubule cell	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	Vasopressin Vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's... --> V2 receptor Arginine vasopressin receptor 2 Arginine vasopressin receptor 2 is a protein that acts as receptor for arginine vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors...		stimulate Epithelial sodium channel Epithelial sodium channel The epithelial sodium channel is a membrane-bound ion-channel that is permeable for Li+-ions, protons and especially Na+-ions. It is a constitutively active ion-channel... (perhaps only minor effect)
Inner medullary collecting duct cell	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	Vasopressin Vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's... --> V2 receptor Arginine vasopressin receptor 2 Arginine vasopressin receptor 2 is a protein that acts as receptor for arginine vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors...		stimulate urea transporter 1 urea transporter 1 exocytosis
proximal convoluted tubule cell	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	PTH Parathyroid hormone Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids... --> PTH receptor 1		Inhibit NHE3 --> ↓H⁺ secretion
juxtaglomerular cell Juxtaglomerular cell The juxtaglomerular cells are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells in the wall of the afferent arteriole that delivers blood to the glomerulus...	kidney Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...	adrenergic agonists --> β-receptor agonists --> A2 receptor dopamine Dopamine Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their... --> dopamine receptor Dopamine receptor Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.... glucagon Glucagon Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is... --> glucagon receptor Glucagon receptor The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...		renin Renin Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction... secretion

In adipocytes and hepatocytes

Adrenaline and glucagon

Glucagon

Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

affect the activity of protein kinase A by changing the levels of cAMP in a cell via the G-protein mechanism, using adenylate cyclase

Adenylate cyclase

Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

. Protein Kinase A acts to phosphorylate many enzymes important in metabolism. For example, protein kinase A phosphorylates acetyl-CoA carboxylase

Acetyl-CoA carboxylase

Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase...

and pyruvate dehydrogenase

Pyruvate dehydrogenase

Pyruvate dehydrogenase complex is a complex of three enzymes that transform pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the...

. Such covalent modification has an inhibitory effect on these enzymes, thus inhibiting lipogenesis

Lipogenesis

Lipogenesis is the process by which acetyl-CoA is converted to fats. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis, the energy can be efficiently stored in the form of fats...

and promoting net gluconeogenesis

Gluconeogenesis

Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

. Insulin, on the other hand, decreases the level of phosphorylation of these enzymes, which instead promotes lipogenesis. Recall that gluconeogenesis does not occur in myocytes.

In nucleus accumbens neurons

PKA helps transfer/translate the dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

signal into cells. It has been found (postmortem) to be elevated in the brains of smokers, in the nucleus accumbens

Nucleus accumbens

The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, which mediates reward and motivation: a part of the brain acted on by "virtually all" recreational drugs, as well as "in the area of the midbrain that responds to dopamine, which acts as a 'reward chemical' in smokers and former-smokers."

External links

Drosophila cAMP-dependent protein kinase 1 - The Interactive Fly

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