Biomaterial Database

Activation of PI 3-kinase in 3T3-L1 adipocytes by association with insulin receptor substrate-1. 1994

L Lamphere, and C L Carpenter, and Z F Sheng, and R G Kallen, and G E Lienhard

Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755.

Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin receptor substrate-1 (IRS-1) on tyrosine. The phosphotyrosine [Tyr(P)] form of IRS-1 then complexes with the enzyme phosphatidylinositol (PI) 3-kinase. In this study, we have investigated the effect of this association on PI 3-kinase activity in 3T3-L1 adipocytes. Insulin stimulated cytosolic PI 3-kinase activity about sevenfold. This stimulation was maximal after 1 min of exposure of cells to insulin, persisted for at least 1 h, and occurred over the range of insulin concentrations that saturate its receptor. By means of immunoprecipitation of IRS-1, it was shown that virtually all of the enhanced activity was due to PI 3-kinase complexed with IRS-1. Moreover, the purified Tyr(P) form of IRS-1, either isolated from 3T3-L1 adipocytes or obtained by phosphorylation of the recombinant protein with the insulin receptor, markedly stimulated the activity of purified rat liver PI 3-kinase. These results show that the association of Tyr(P) IRS-1 with PI 3-kinase activates the enzyme and thereby can explain the elevation of PI 3,4-bisphosphate and PI 3,4,5-trisphosphate in vivo observed upon treatment of adipocytes with insulin.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D010750	Phosphoproteins		Phosphoprotein
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D014443	Tyrosine	A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.	L-Tyrosine,Tyrosine, L-isomer,para-Tyrosine,L Tyrosine,Tyrosine, L isomer,para Tyrosine
D017667	Adipocytes	Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.	Fat Cells,Lipocytes,Adipocyte,Cell, Fat,Cells, Fat,Fat Cell,Lipocyte
D055504	Insulin Receptor Substrate Proteins	A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share an N-terminal PLECKSTRIN HOMOLOGY DOMAIN, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation, insulin receptor substrate proteins interact with specific SH2 DOMAIN containing proteins that are involved in insulin receptor signaling.	IRS Signaling Adaptor Proteins,Insulin Receptor Substrate-1,Insulin Receptor Substrate-1 Protein,Insulin Receptor Substrate-2,Insulin Receptor Substrate-2 Protein,Insulin Receptor Substrate-3,Insulin Receptor Substrate-3 Protein,Insulin Receptor Substrate-4,Insulin Receptor Substrate-4 Protein,Insulin Receptor Substrate 1,Insulin Receptor Substrate 1 Protein,Insulin Receptor Substrate 2,Insulin Receptor Substrate 2 Protein,Insulin Receptor Substrate 3,Insulin Receptor Substrate 3 Protein,Insulin Receptor Substrate 4,Insulin Receptor Substrate 4 Protein
D017853	Phosphotransferases (Alcohol Group Acceptor)	A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
D019000	Phosphotyrosine	An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.	Tyrosine-O-phosphate,Tyrosine O phosphate