Regulation of adaptor protein GIT1 in platelets, leading to the interaction between GIT1 and integrin alpha(IIb)beta3.
GIT1 is an adaptor protein, which links signaling proteins to focal adhesion, thereby regulating cytoskeletal reorganization. Platelets undergo dynamic cytoskeletal reorganization during platelet activation, for which a large number of adaptor proteins are required. However, there has been no report of GIT1 in platelets. We found that GIT1 was abundantly expressed in platelets and underwent tyrosine phosphorylation downstream of integrin alpha(IIb)beta(3), which was inhibited by the Src kinase inhibitor PP2. Furthermore, GIT1 constitutively associated with betaPIX, a guanine nucleotide exchange factor (GEF) for Rac. The GIT1/betaPIX complex associated with alpha(IIb)beta(3), concomitantly with GIT1 tyrosine phosphorylation. Moreover, both GIT1 and alpha(IIb)beta(3) rapidly translocated to the cytoskeletal fraction during platelet aggregation, which was not observed in the absence of aggregation. These results suggest that tyrosine phosphorylation of GIT1 by Src kinases may regulate cytoskeletal reorganization downstream of alpha(IIb)beta(3) by bringing the Rac GEF betaPIX to the vicinity of the integrin.
Sato
Hitomi
H
Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Suzuki-Inoue
Katsue
K
Inoue
Osamu
O
Ozaki
Yukio
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D019000:Phosphotyrosine / Q000378:metabolism; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D064067:Rho Guanine Nucleotide Exchange Factors; D019000:Phosphotyrosine; D019061:src-Family Kinases