[Sequence homology in the primary structures of tyrosine kinase receptors of insulin superfamily and protein substrates of insulin type I and type II receptors].
Ligand-activated tyrosine kinase receptors of insulin superfamily peptides can realize the signal transduction to SH2-proteins (phosphatidylinositol 3-kinase, PI3K), protein phosphotyrosine phosphatase (PPTP), GRB2-adaptor protein in two pathways: 1) with participation of specific proteins--insulin receptor substrates 1 and 2 (IRS1/IRS2); and 2) direct interaction between receptors and SH2-proteins (without IRS-proteins). Consequently, structural related determinants, which are responsible for the interaction with SH2-proteins, must be present in the receptor and IRS molecules. The comparative analysis of amino acid sequences (AAS) of human receptors of insulin, insulin-like growth factor-I and insulin-related peptide and AAS of IRS1/IRS2 proteins allow one to identify for the first time the long homologous regions in their primary structures. After alignment of AAS of the regions, the sited-targets for tyrosine phosphorylation, most important for functional activity of tyrosine kinase receptors and IRS proteins, coincided with each other. These results show that some homologous regions can have similar function. Thus, the regions can involve in coupling the receptors and IRS-proteins with SH2-proteins, such as PI3K, PPTP, GRB2-adaptor protein. It is also possible that the homologous regions of tyrosine kinase receptors and IR1/IRS2 proteins mediate the interaction between their proteins.
Shpakov
A O
AO
I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D066246:ErbB Receptors / Q000737:chemistry; D051380:GRB2 Adaptor Protein; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D011972:Receptor, Insulin / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases
Gomologichnye posledovatel'nosti v pervichnykh strukturakh retseptorov tirozinkinaz insulinovogo supersemeĭstva i belkov-substratov 1 i 2 insulinovogo retseptora.