[Search for a molecular determinant in phosphatidylinositol-3-kinase molecules, involved in the interaction with the beta-gamma-G protein dimer].
The heterodimer p85/p110 and p101/p120 gamma phosphatidylinositol-3-kinases (PI3K) are important effector proteins in the signal transduction in a cell. beta gamma-subunits of heterotrimetic G-proteins are some of the main regulators of PI3K functional activity. Molecular determinants in the molecules of PI3K which may be responsible for coupling with beta gamma-dimer, remain obscure. The aim of this work was to identify the determinants of the basis of a comparative analysis of primary structures of PI3K and other beta gamma-binding proteins (adenylyl cyclases of the different types, G-protein-coupled receptor kinases, phospholypase C beta). The obtained data enables us to make some conclusions. In p85/p110 PI3K, beta gamma-binding determinants are located mainly in its regulatory subunit (BCR-domain, inter-SH2-domain). However, the interaction between beta gamma and catalytic domain of the catalytic p-110 subunit is also possible. In p101/p120 gamma PI3K, beta gamma-binding regions are located only in the catalytic p120 gamma-subunit of the enzyme, i.e. in its middle part and C-terminal catalytic domain regions of 436-502, 791-822 and 911-1000). In spite of the fact that potential beta gamma-binding regions are localized in different loci of PI3K subunits, they can form a compact beta gamma-binding surface in the process of its molecule folding, similar by as in other beta gamma-binding proteins.
Shpakov
A O
AO
Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg. shpakov@hormone.ief.spb.su
D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins
Poisk molekuliarnykh determinant v molekulakh fosfatidilinozitol-3-kinaz, vovlechennykh vo vzaimodeĭstvie s beta-gamma-dimerom G-belka.