Is IRS-1 an adaptor protein?
Is IRS-1 an adaptor protein?
Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the IRS-1 gene. It is a 131 kDa protein with amino acid sequence of 1242 residues.
What are IRS molecules?
Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and play a central role in maintaining basic cellular functions such as growth, survival, and metabolism.
What does IRS do insulin?
The IRS proteins are a family of cytoplasmic adaptor proteins that transmit signals from the insulin and IGF-1 receptors to elicit a cellular response.
Does IRS have SH2 domain?
IRS-1 also interacts with other proteins such as SHPTP2, a novel SH2 domain-containing Tyr phosphatase, and GRB-2/sem-5, a protein that is implicated in p21ras signaling. The interaction between phosphorylated IRS-1 and multiple SH2 domain-containing proteins may ultimately explain the pleiotropic effects of insulin.
Is IRS-1 a kinase?
IRS1 signaling pathway. IRS1 is recruited by its PH/PTB domains and phosphorylated in tyrosine residues (pY) by upstream tyrosine kinase receptors. Tyrosine phosphorylated IRS1 binds to signaling effectors and activates signaling cascades, regulating several biological processes, including proliferation and survival.
How does IRS-1 activate PI3K?
The phosphorylated IRS contains a SH2 domain junction, which binds to the PI3K regulatory subunit P85, activates PI3K, and regulates the downstream factor Akt, and ultimately leads to GLUT4 translocation to promote the utilization of glucose and lower body blood glucose [25].
What other proteins does insulin interact with?
Most insulin effects appear to be mediated through the interaction of IRS-1 and -2, and Shc, with the insulin receptor (81, 82, 85). Other docking proteins like CBL, APS, SH2B, GAB1 and-2 and DOCK1 and-2 have been less extensively studied (81).
What is IRS-1?
Tyrosine phosphorylated IRS1 binds to signaling effectors and activates signaling cascades, regulating several biological processes, including proliferation and survival. IRS1 is an intracellular signaling adaptor protein that integrates and coordinates numerous biologically key extracellular signals within the cell.
What role does a PTB domain play in insulin receptor signaling?
Phosphotyrosine binding (PTB) domains of the adaptor protein Shc and insulin receptor substrate (IRS-1) interact with a distinct set of activated and tyrosine-phosphorylated cytokine and growth factor receptors and play important roles in mediating mitogenic signal transduction.
How does IRS1 activate PI3K?
How is the insulin receptor activated?
The addition of the phosphate groups generates a binding site for the insulin receptor substrate (IRS-1), which is subsequently activated via phosphorylation. The activated IRS-1 initiates the signal transduction pathway and binds to phosphoinositide 3-kinase (PI3K), in turn causing its activation.
How is IRS-1 immunoprecipitated from a supernatant?
IRS-1 was immunoprecipitated from an aliquot of the supernatant (500 μg), as described above for the PI 3-kinase analysis, and proteins were separated by SDS-PAGE. After transfer, membranes were probed with a polyclonal antibody against phospho-Ser (312) or phospho-Ser (616) (Cell Signaling).
What happens to IRS-1 in kidney transplant recipients?
Basal IRS-1 Ser (312) and Ser (616) phosphorylation was also increased in nondiabetic kidney transplant recipients. Insulin increased phosphorylation of IRS-1 at Ser (312) but not Ser (616) in healthy subjects, with impairments noted in nondiabetic kidney and pancreas-kidney transplant recipients.
How to immunoprecipitate IRS-1 from MCF-7 cells?
Immunoprecipitation of IRS-1 from insulin treated MCF-7 cell extracts using IRS-1 antibody (Lane1). Lane 2: No antibody control. Lane 3: Input control Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.
