Abstract
Ligand stimulation of growth factor receptors with intrinsic protein-tyrosine kinase activity initiates the assembly of multienzyme signalling complexes. This is mediated by binding of proteins with
src
homology 2 (SH2) domains to receptor autophosphorylation sites. Among the proteins involved in complex formation is phosphatidylinositol (PI) 3-kinase, a heterodimeric enzyme composed of 85 kDa and 110 kDa subunits, which binds to receptor (and non-receptor) phosphotyrosine residues through the two SH2 domains in the p85 subunit. p85 acts as an adaptor protein and possibly a regulator of the p110 catalytic subunit that phosphorylates phosphoinositides at the D-3 position of the inositol ring. p85 subunit is composed of several distinct functional domains: one SH3 and two SH2 domains, a p110 binding site and a region with homology to BCR. Expression of these domains in
E. coli as
GST-fusion proteins has allowed definition by nuclear magnetic resonance (NMR) of three-dimensional structures for the SH2 and SH3 domains. The relationship of structure to function for these domains is discussed. The p110 catalytic domain has a region of homology with vps34p of
Saccharomyces cerevisiae
, a protein involved in protein sorting to the yeast vacuole. Possible clues to the function of PI 3-kinase derived from this and other observations are presented.
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology
Reference38 articles.
1. Binding of SH2 Domains of Phospholipase Cγ1, GAP, and Src to Activated Growth Factor Receptors
2. Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerivisiae J . biol;Auger K.R.;Chem.,1989
3. Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation;Backer J.M .;E M BO J .,1992
4. Structure of an SH2 domain of the p85α subunit of phosphatidylinositol-3-OH kinase
5. Oncogenes and signal transduction
Cited by
44 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献