The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1.
RACK1 is an intracellular receptor for the serine/ threonine protein kinase C. Previously, we demonstrated that RACK1 also interacts with the Src protein-tyrosine kinase. RACK1, via its association with these protein kinases, may play a key role in signal transduction. To further characterize the Src-RACK1 interaction and to analyze mechanisms by which cross-talk occurs between the two RACK1-linked signaling kinases, we identified sites on Src and RACK1 that mediate their binding, and factors that regulate their interaction. We found that the interaction of Src and RACK1 is mediated, in part, by the SH2 domain of Src and by phosphotyrosines in the sixth WD repeat of RACK1, and is enhanced by serum or platelet-derived growth factor stimulation, protein kinase C activation, and tyrosine phosphorylation of RACK1. To the best of our knowledge, this is the first report of tyrosine phosphorylation of a member of the WD repeat family of proteins. We think that tyrosine phosphorylation of these proteins is an important mechanism of signal transduction in cells.
Department of Medicine, Stanford University, Stanford, California 94305, USA.
B Y
BY
Chang
M
M
Chiang
C A
CA
Cartwright
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001769:Blood; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers; D004789:Enzyme Activation; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D014443:Tyrosine / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
D017931:DNA Primers; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D000075370:Receptors for Activated C Kinase; D020703:ras GTPase-Activating Proteins; C070301:peptide I; D014443:Tyrosine; D019061:src-Family Kinases; D011493:Protein Kinase C