Docking protein Gab2 positively regulates glycoprotein VI-mediated platelet activation.
Gab2, a recently identified docking protein, contains a pleckstrin homology domain and potential binding sites for SH2 and SH3 domain-containing proteins. Gab2 has been shown to support growth, differentiation, and function in a number of haematopoietic cells, although its role in platelets remains to be determined. Here we report that cross-linking of the collagen receptor GPVI by the snake venom toxin convulxin stimulates tyrosine phosphorylation of Gab2. Furthermore, platelet aggregation induced by submaximal concentrations of convulxin is attenuated in the absence of Gab2, although recovery is seen with higher concentrations of the toxin. Consistent with this, tyrosine phosphorylation of Fc receptor gamma-chain, Syk, Btk, and phospholipase Cgamma2 by convulxin is reduced in the absence of Gab2. In comparison, the G protein-coupled receptor agonist, thrombin, does not induce phosphorylation of Gab2 and aggregation is unaltered in the absence of the toxin. These findings provide evidence for a functional role of Gab2 in supporting platelet activation by GPVI.
Yi
Qun
Q
Department of Clinical and Laboratory Medicine, Faculty of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho, Nakakoma, Japan.
Suzuki-Inoue
Katsue
K
Asazuma
Naoki
N
Inoue
Osamu
O
Watson
Steve P
SP
Ozaki
Yukio
Y
D048868:Adaptor Proteins, Signal Transducing; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D003435:Crotalid Venoms; C490895:GAB2 protein, human; D037181:Lectins, C-Type; D010750:Phosphoproteins; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D014443:Tyrosine; D013917:Thrombin