There is extensive evidence that FcR gamma-chain couples to the collagen receptor glycoprotein VI (GPVI) and becomes phosphorylated on tyrosines upon receptor cross-linking. However, it is not established whether this receptor complex is sufficient to initiate the signalling cascade. We transfected GPVI and the FcR gamma-chain into the human erythroleukaemia cell line K562, which lacks detectable expression of GPVI and the FcR gamma-chain.
View Article and Find Full Text PDFIn this study, we show that the G protein-coupled receptor agonist thrombin, the glycoprotein VI agonist convulxin, and the cytokine receptor Mpl agonist thrombopoietin (TPO) are able to induce activation of RAS in human platelets. Recruitment of GRB2 by tyrosine-phosphorylated proteins in response to TPO and convulxin but not by thrombin occurred with a similar time-course to RAS activation, consistent with a causal relationship. On the other hand, activation of ERK2 by thrombin and convulxin is delayed and also inhibited by the protein kinase C inhibitor Ro-31 8220, whereas RAS activation is unaffected.
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