Insulin receptor substrate 1 (IRS-1) is a 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...

 that in humans is encoded by the IRS-1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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Function

Insulin receptor substrate

Insulin receptor substrate

Insulin receptor substrate is an important ligand in the insulin response of human cells.IRS-1, for example, is an IRS protein which contains a phosphotyrosine binding-domain . In addition, the insulin receptor contains a NPXpY domain. The PTB-domain binds the NPXpY domain...

 1 plays a key role in transmitting signals from the insulin

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 and insulin-like growth factor-1 (IGF-1

Insulin-like growth factor 1

Insulin-like growth factor 1 also known as somatomedin C is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a "sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" in the 1970s.IGF-1 is a hormone similar in molecular...

) receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

s to intracellular pathways PI3K

Phosphoinositide 3-kinase

Phosphatidylinositol 3-kinases are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In response to lipopolysaccharide, PI3K phosphorylates p65, inducing...

 / Akt

AKT

Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...

 and Erk

Extracellular signal-regulated kinases

In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...

 MAP kinase

Mitogen-activated protein kinase

Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...

 pathways.

Tyrosine 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 the insulin receptors or IGF-1 receptors, upon extracellular ligand

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

 binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its SH2 domain

SH2 domain

The SH2 domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins...

s. Multiple tyrosine residues of IRS-1 itself are then phosphorylated by these receptors. This enables IRS-1 to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway

MAPK/ERK pathway

The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...

.

IRS-1 plays important biological function for both metabolic and mitogen

Mitogen

A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....

ic (growth promoting) pathways: mice deficient of IRS1 have only a mild diabetic phenotype

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

, but a pronounced growth impairment, i.e., IRS-1 knockout mice

Knockout mouse

A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

 only reach 50% of the weight of normal mice. IRS-1 may also play a role in cancer, as it has been shown that transgenic mice overexpressing IRS-1 develop breast cancer.

Regulation

The cellular protein levels of IRS-1 are regulated by the Cullin7

CUL7

Cullin-7 is a protein that in humans is encoded by the CUL7 gene.-External Links:* *...

 E3 ubiquitin ligase

Ubiquitin ligase

A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...

, which targets IRS-1 for ubiquitin

Ubiquitin

Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

 mediated degradation by the proteasome

Proteasome

Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria.  In eukaryotes, they are located in the nucleus and the cytoplasm.  The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...

.

Interactions

IRS1 has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with PTPN11

PTPN11

Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.PTPN11 is a member of the protein tyrosine phosphatase ...

, Janus kinase 2

Janus kinase 2

Janus kinase 2 is a human protein that has been implicated in signaling by members of the type II cytokine receptor family , the GM-CSF receptor family , the gp130 receptor family , and the single chain receptors...

, Insulin-like growth factor 1 receptor, Grb2

Grb2

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....

, PIK3R3

PIK3R3

Phosphatidylinositol 3-kinase regulatory subunit gamma is an enzyme that in humans is encoded by the PIK3R3 gene.-Interactions:PIK3R3 has been shown to interact with Insulin-like growth factor 1 receptor, IRS1 and Retinoblastoma protein....

, Janus kinase 1

Janus kinase 1

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain of type I cytokine receptors, to elicit signals from the IL-2 receptor family , the IL-4 receptor family , the gp130 receptor family JAK1 is a human...

, PTK2

PTK2

PTK2 protein tyrosine kinase 2 , also known as Focal Adhesion Kinase , is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes...

, PTPN1

PTPN1

Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B is an enzyme that is the founding member of the protein tyrosine phosphatase family. In humans it is encoded by the PTPN1 gene...

, MAPK8

MAPK8

Mitogen-activated protein kinase 8 is an enzyme that in humans is encoded by the MAPK8 gene.-Interactions:MAPK8 has been shown to interact with SPIB, DUSP1, Activating transcription factor 2, SH3BP5, GSTP1, MAPK8IP1, MAP2K7, CRK, MAP2K4, DUSP22, Myc, MAP3K2, DUSP10, REL, MAPK8IP3, IRS1, MAP3K1 and...

, Bcl-2

Bcl-2

Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...

, Insulin receptor

Insulin receptor

In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....

, PIK3R1

PIK3R1

Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.-Interactions:PIK3R1 has been shown to interact with EPH receptor A2, KHDRBS1, Lymphocyte cytosolic protein 2, Janus kinase 2, GAB2, CD117, BCAR1, CD28, SHB, EZR, PIK3CD, GAB1, HRAS,...

 and YWHAE

YWHAE

14-3-3 protein epsilon is a protein that in humans is encoded by the YWHAE gene.-Interactions:YWHAE has been shown to interact with CDC25B, Insulin-like growth factor 1 receptor, NGFRAP1, TGF beta 1, HERG, C-Raf, NDEL1, HDAC4, IRS1 and MAP3K3....

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Further reading