Identification of a molecular recognition role for the activation loop phosphotyrosine of the SRC tyrosine kinase.
A human cDNA phage display library screen, using a phosphopeptide designed to mimic the activation loop phosphotyrosine of the Src tyrosine kinase, has identified the N-terminal SH2 domain of the p85 regulatory subunit of phosphatidyl inositol-3 kinase (PI3K) as an interacting recognition domain. Activation loop phosphorylation is known to play a conformational role in kinase activation, but is largely not thought to play a role in protein/protein recognition. Affinity chromatography and biochemical evaluation in mouse fibroblast cells has confirmed the dependence of this interaction on both the Src activation loop phosphotyrosine and the N-terminal SH2 domain of PI3K.
Videlock
Elizabeth J
EJ
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Chung
Victor K
VK
Hall
Justin M
JM
Hines
John
J
Agapakis
Christina M
CM
Austin
David J
DJ
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D019000:Phosphotyrosine / Q000031:analogs & derivatives / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism*
D010748:Phosphopeptides; D019000:Phosphotyrosine; D001710:Biotin; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases