Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation.
CrkII is an intracellular adaptor protein involved in signal transduction by various growth factors. Activation of PDGF alpha-receptor resulted in its association with CrkII in vivo. In contrast, binding of CrkII to the PDGF beta-receptor was negligible, despite its becoming prominently phosphorylated. Bacterially expressed GST-CrkII SH2 domain specifically bound to Tyr-762 and Tyr-771 in the activated PDGF alpha- and beta- receptors, respectively. GST fusion protein of full-length CrkII also bound to the activated PDGF beta-receptor. However, tyrosine phosphorylation of GST-CrkII diminished its binding to the beta-receptor. CrkI, a truncated version of CrkII lacking the phosphorylatable tyrosine residue, could bind to both PDGF alpha- and beta-receptors in vivo. In conclusion, tyrosine phosphorylation of CrkII negatively affects its binding to the PDGF receptors. The differential binding of CrkII to the PDGF alpha- and beta- receptors may be a rationale for functional diversity between the two receptors.
Matsumoto
T
T
Second Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
Yokote
K
K
Take
A
A
Takemoto
M
M
Asaumi
S
S
Hashimoto
Y
Y
Matsuda
M
M
Saito
Y
Y
Mori
S
S
D000818:Animals; D008954:Models, Biological; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D011494:Protein Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta