Protein kinase C
Encyclopedia
Protein kinase
C also known as PKC is a family of enzyme
s that are involved in controlling the function of other protein
s through the phosphorylation
of hydroxyl
groups of serine
and threonine
amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol or Ca2+. Hence PKC enzymes play important roles in several signal transduction
cascades.
The PKC family consists of about ten isozymes. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, diacylglycerol
(DAG), and a phospholipid
such as phosphatidylserine
for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for activation. Thus, conventional and novel PKCs are activated through the same signal transduction
pathway as phospholipase C
. On the other hand, atypical (a)PKCs (including protein kinase Mζ and ι / λ isoforms) require neither Ca2+ nor diacylglycerol for activation. The term "protein kinase C" usually refers to the entire family of isoforms.
/threonine
kinases. The second messenger requirement differences in the isoforms are a result of the regulatory region, which are similar within the classes, but differ among them. Most of the crystal structure of the catalytic region of PKC has not been determined, except for PKC theta and iota. Due to its similarity to other kinases whose crystal structure have been determined, the structure can be strongly predicted.
Another feature of the PKC catalytic region that is essential to the viability of the kinase is its phosphorylation. The conventional and novel PKCs have three phosphorylation sites, termed: the activation loop, the turn motif, and the hydrophobic motif. The atypical PKCs are phosphorylated only on the activation loop and the turn motif. Phosphorylation of the hydrophobic motif is rendered unnecessary by the presence of a glutamic acid in place of a serine, which, as a negative charge, acts similar in manner to a phosphorylated residue. These phosphorylation events are essential for the activity of the enzyme, and 3-phosphoinositide-dependent protein kinase-1 (PDK1
) is the upstream kinase responsible for initiating the process by transphosphorylation of the activation loop.(Balendran et al., 2000)
The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids close to the Ser/Thr to be phosphorylated. Their substrates are, e.g., MARCKS protein
s, MAP kinase, transcription factor inhibitor IκB, the vitamin D
3 receptor VDR, Raf kinase
, calpain
, and the epidermal growth factor receptor
.
s (membrane-bound receptor for activated protein kinase C proteins). The protein kinase C enzymes are known for their long-term activation: They remain activated after the original activation signal or the Ca2+-wave is gone. This is presumably achieved by the production of diacylglycerol from phosphatidylinositol by a phospholipase
; fatty acids may also play a role in long-term activation.
A multiplicity of functions have been ascribed to PKC. Recurring themes are that PKC is involved in receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory. These functions are achieved by PKC mediated phosphorylation of other proteins. However, the substrate proteins present for phosphorylation vary, since protein expression is different between different kinds of cells. Thus, effects of PKC are cell-type specific:
, may potentially be beneficial in peripheral diabetic retinopathy
.
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
C also known as PKC is 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 that are involved in controlling the function of other 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...
s through the phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
groups of 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:...
and 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...
amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol or Ca2+. Hence PKC enzymes play important roles in several signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
cascades.
The PKC family consists of about ten isozymes. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, diacylglycerol
Diglyceride
A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
(DAG), and a phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
such as phosphatidylserine
Phosphatidylserine
Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for activation. Thus, conventional and novel PKCs are activated through the same signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
pathway as phospholipase C
Phospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
. On the other hand, atypical (a)PKCs (including protein kinase Mζ and ι / λ isoforms) require neither Ca2+ nor diacylglycerol for activation. The term "protein kinase C" usually refers to the entire family of isoforms.
Isozymes
- conventional - require DAG, Ca2+, and phospholipid for activation
- PKC-αPKC alphaProtein kinase C alpha , also known as PRKCA, refers to both a human gene and the protein that is encoded by it.-Background:...
- PKC-βIPRKCB1Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene..-Interactions:PRKCB1 has been shown to interact with RIPK4, Beta adrenergic receptor kinase, PDLIM5 and GNB2L1.-Further reading:-See also:*Protein kinase C...
- PKC-βII
- PKC-γPRKCGProtein kinase C gamma type is an enzyme that in humans is encoded by the PRKCG gene.-External Links:* -Further reading:...
- PKC-α
- novel - require DAG but not Ca2+ for activation
- PKC-δPRKCDProtein kinase C delta type is an enzyme that in humans is encoded by the PRKCD gene.- Function :Protein kinase C is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol...
- PKC-εPRKCEProtein kinase C epsilon type is an enzyme that in humans is encoded by the PRKCE gene.- Function :Protein kinase C is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol...
- PKC-η
- PKC-θPRKCQProtein kinase C theta type is an enzyme that in humans is encoded by the PRKCQ gene.-Interactions:PRKCQ has been shown to interact with FYN, GLRX3, AKT1 and VAV1.PRKCQ has been shown to phosphorylate CARD11 as part of the NF-κB signaling pathway....
- PKC-δ
- atypical - require neither Ca2+ nor DAG for activation
- PKC-ιPRKCIProtein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.-Interactions:PRKCI has been shown to interact with Glyceraldehyde 3-phosphate dehydrogenase, Centaurin, alpha 1, Phosphoinositide-dependent kinase-1, FRS2, SMG1 , Sequestosome 1 and PARD3.-Further reading:...
- PKC-ζ
- PK-N1
- PK-N2
- PKC-ι
Structure
The structure of all PKCs consists of a regulatory domain and a catalytic domain tethered together by a hinge region. The catalytic region is highly conserved among the different isoforms, as well as, to a lesser degree, among the catalytic region of other serineSerine
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:...
/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...
kinases. The second messenger requirement differences in the isoforms are a result of the regulatory region, which are similar within the classes, but differ among them. Most of the crystal structure of the catalytic region of PKC has not been determined, except for PKC theta and iota. Due to its similarity to other kinases whose crystal structure have been determined, the structure can be strongly predicted.
Regulatory
The regulatory domain or the amino-teminus of the PKCs contains several shared subregions. The C1 domain, present in all of the isoforms of PKC has a binding site for DAG as well as non-hydrolysable, non-physiological analogues called phorbol esters. This domain is functional and capable of binding DAG in both conventional and novel isoforms, however, the C1 domain in atypical PKCs is incapable of binding to DAG or phorbol esters. The C2 domain acts as a Ca2+ sensor and is present in both conventional and novel isoforms, but functional as a Ca2+ sensor only in the conventional. The pseudosubstrate region, which is present in all three classes of PKC, is a small sequence of amino acids that mimic a substrate and bind the substrate-binding cavity in the catalytic domain,lack crital serine, threonine phosphoacceptor residues, keeping the enzyme inactive. When Ca2+ and DAG are present in sufficient concentrations, they bind to the C2 and C1 domain, respectively, and recruit PKC to the membrane. This interaction with the membrane results in release of the pseudosubstrate from the catalytic site and activation of the enzyme. In order for these allosteric interactions to occur, however, PKC must first be properly folded and in the correct conformation permissive for catalytic action. This is contingent upon phosphorylation of the catalytic region, discussed below.Catalytic
The catalytic region or kinase core of the PKA allows for different functions to be processed; PKB (also known as Akt) and PKC kinases contains approximately 40% amino acid sequence similarity. This similarity increases to ~ 70% across PKCs and even higher when comparing within classes. For example, the two atypical PKC isoforms, ζ and ι/λ, are 84% identical (Selbie et al., 1993). Of the over-30 protein kinase structures whose crystal structure has been revealed, all have the same basic organization. They are a bilobal structure with a β sheet comprising the N-terminal lobe and an α helix constituting the C-terminal lobe. Both the ATP- and substrate-binding sites are located in the cleft formed by these two lobes. This is also where the pseudosubstrate domain of the regulatory region binds.Another feature of the PKC catalytic region that is essential to the viability of the kinase is its phosphorylation. The conventional and novel PKCs have three phosphorylation sites, termed: the activation loop, the turn motif, and the hydrophobic motif. The atypical PKCs are phosphorylated only on the activation loop and the turn motif. Phosphorylation of the hydrophobic motif is rendered unnecessary by the presence of a glutamic acid in place of a serine, which, as a negative charge, acts similar in manner to a phosphorylated residue. These phosphorylation events are essential for the activity of the enzyme, and 3-phosphoinositide-dependent protein kinase-1 (PDK1
PDK1
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the PDK1 gene. It codes for an isozyme of pyruvate dehydrogenase kinase ....
) is the upstream kinase responsible for initiating the process by transphosphorylation of the activation loop.(Balendran et al., 2000)
The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids close to the Ser/Thr to be phosphorylated. Their substrates are, e.g., MARCKS protein
MARCKS protein
MARCKS proteins play important roles in cell shape, cell motility, secretion, transmembrane transport, and regulation of the cell cycle...
s, MAP kinase, transcription factor inhibitor IκB, the vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
3 receptor VDR, Raf kinase
Raf kinase
Raf kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse sarcoma virus 3611 contains a Raf kinase-related oncogene that enhances fibrosarcoma induction...
, calpain
Calpain
A calpain is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database...
, and the epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
.
Activation
Upon activation, protein kinase C enzymes are translocated to the plasma membrane by RACK proteinRACK protein
RACK is an acronym for Receptor for Activated C-Kinase and is responsible for the binding of active forms of the protein kinase C family of enzymes...
s (membrane-bound receptor for activated protein kinase C proteins). The protein kinase C enzymes are known for their long-term activation: They remain activated after the original activation signal or the Ca2+-wave is gone. This is presumably achieved by the production of diacylglycerol from phosphatidylinositol by a phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
; fatty acids may also play a role in long-term activation.
Function
A multiplicity of functions have been ascribed to PKC. Recurring themes are that PKC is involved in receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory. These functions are achieved by PKC mediated phosphorylation of other proteins. However, the substrate proteins present for phosphorylation vary, since protein expression is different between different kinds of cells. Thus, effects of PKC are cell-type specific:
| Cell type | Organ/system | Activators ligands --> Gq Gq alpha subunit Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway... -GPCRs |
Effects |
|---|---|---|---|
| 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... cell (gastrointestinal tract Gastrointestinal tract The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. .... sphincter Sphincter A sphincter is an anatomical structure, or a circular muscle, that normally maintains constriction of a natural body passage or orifice and which relaxes as required by normal physiological functioning... s) |
digestive system |
|
contraction |
| 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... cells in: Iris dilator muscle The iris dilator muscle , is a smooth muscle of the eye, running radially in the iris and therefore fit as a dilator. It has its origin from the anterior epithelium. It is innervated by the sympathetic system, which acts by releasing noradrenaline, which acts on α1-receptors... (sensory system Sensory system A sensory system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory receptors, neural pathways, and parts of the brain involved in sensory perception. Commonly recognized sensory systems are those for vision, hearing, somatic... ) Urethral sphincter The term urethral sphincter refers to one of two muscles used to control the exit of urine in the urinary bladder through the urethra. The two muscles are the external urethral sphincter and the internal urethral sphincter... (urinary system Urinary system The urinary system is the organ system that produces, stores, and eliminates urine. In humans it includes two kidneys, two ureters, the bladder and the urethra.-Kidney:... ) Uterus The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species... (reproductive system Reproductive system The reproductive system or genital system is a system of organs within an organism which work together for the purpose of reproduction. Many non-living substances such as fluids, hormones, and pheromones are also important accessories to the reproductive system. Unlike most organ systems, the sexes... ) Integumentary system The integumentary system is the organ system that protects the body from damage, comprising the skin and its appendages... ) Ureter In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter.... (urinary system Urinary system The urinary system is the organ system that produces, stores, and eliminates urine. In humans it includes two kidneys, two ureters, the bladder and the urethra.-Kidney:... ) Urinary bladder The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor... (urinary system Urinary system The urinary system is the organ system that produces, stores, and eliminates urine. In humans it includes two kidneys, two ureters, the bladder and the urethra.-Kidney:... ) |
Various |
|
contraction |
| 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... cells in: Ciliary muscle The ciliary muscle is a ring of striated smooth muscle in the eye's middle layer that controls accommodation for viewing objects at varying distances and regulates the flow of aqueous humour into Schlemm's canal. It changes the shape of the lens within the eye not the size of the pupil which is... |
sensory system Sensory system A sensory system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory receptors, neural pathways, and parts of the brain involved in sensory perception. Commonly recognized sensory systems are those for vision, hearing, somatic... |
acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M3 receptor |
contraction |
| 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... cell (vascular) |
circulatory system Circulatory system The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc... |
5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... |
Vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in... |
| 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... cell (seminal tract Seminal tract The seminal tract is a part of the male reproductive system and consists of Seminiferous tubules , Epididymis , Vas deferens and Ejaculatory duct.... ) |
reproductive system Reproductive system The reproductive system or genital system is a system of organs within an organism which work together for the purpose of reproduction. Many non-living substances such as fluids, hormones, and pheromones are also important accessories to the reproductive system. Unlike most organ systems, the sexes... |
|
ejaculation Ejaculation Ejaculation is the ejecting of semen from the male reproductory tract, and is usually accompanied by orgasm. It is usually the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. In rare cases ejaculation occurs because of prostatic disease... |
| 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... cell (GI tract Gastrointestinal tract The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. .... ) |
digestive system |
5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... or 5-HT2B receptor 5-HT2B receptor 5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:... Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... (ACh) --> M3 receptor |
|
| 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... cell (bronchi) |
respiratory system Respiratory system The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles... |
5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M3 and M1 receptor |
bronchoconstriction Bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus.... |
| 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... |
|
|
| neurons in autonomic ganglia | 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... |
acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M1 receptor |
EPSP Excitatory postsynaptic potential In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels... |
| neurons in CNS Central nervous system The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish... |
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... |
5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M1 receptor |
|
| platelet Platelet Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days... s |
circulatory system Circulatory system The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc... |
5-HT --> 5-HT2A receptor 5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... |
aggregation |
| ependymal cells (choroid plexus Choroid plexus The choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced... ) |
ventricular system Ventricular system The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.-Components:The system comprises four ventricles:* right and left lateral ventricles* third ventricle... |
5-HT --> 5-HT2C receptor 5-HT2C receptor The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the... |
↑cerebrospinal fluid Cerebrospinal fluid Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord... secretion |
| heart muscle | circulatory system Circulatory system The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc... |
|
positive ionotropic effect Ionotropic effect An ionotropic effect is a special kind of effect of a hormone on its target. The hormone activates or deactivates ionotropic receptors . The effect can be either positive or negative, whether the effect is a depolarization or a hyperpolarization respectively.-Examples:Noradrenaline An ionotropic... |
| serous cells (salivary gland Salivary gland The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose... ) |
digestive system |
Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M1 and M3 receptors |
Potassium Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are... levels. |
| serous cells (lacrimal gland Lacrimal gland The lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called... ) |
digestive system |
Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M3 receptor |
|
| 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... |
digestive system/endocrine system Endocrine system In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"... |
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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... and 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.... |
| 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... |
digestive system |
|
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... and 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.... |
| sweat gland Sweat gland Sweat glands, or sudoriferous glands, are small tubular structures of the skin that produce sweat. There are two kinds of sweat glands:... cells |
integumentary system Integumentary system The integumentary system is the organ system that protects the body from damage, comprising the skin and its appendages... |
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| parietal cell Parietal cell Parietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.Acetylcholine and gastrin . The histamine receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin receptors increase intracellular Ca2+ levels... s |
digestive system | acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans... --> M1 receptors |
↑ gastric acid Gastric acid Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride... secretion |
Pathology
Protein kinase C, activated by tumor promoter phorbol ester, may phosphorylate potent activators of transcription, and thereby lead to increased expression of oncogenes, promoting cancer progression, or interfere with other phenomena.Inhibitors
Protein kinase C inhibitors, such as ruboxistaurinRuboxistaurin
Ruboxistaurin is an investigational drug for diabetic peripheral retinopathy. It is currently being investigated by Eli Lilly and Company....
, may potentially be beneficial in peripheral diabetic retinopathy
Diabetic retinopathy
Diabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness....
.