Characterisation of Rac activation in thrombin‐ and collagen‐stimulated human blood platelets

Abstract

In this study, we characterised the mechanisms of Rac GTPase activation in human platelets stimulated by two physiological agonists, either thrombin, acting through membrane receptors coupled to heterotrimeric G-proteins, or collagen which is known to mobilise a tyrosine kinase-dependent pathway. Both agonists induced a rapid activation of Rac that was not significantly affected by the inhibition of integrin K K IIb L L 3 engagement. Using pharmacological inhibitors, we found that phospholipase C activation and calcium mobilisation were essential for platelet Rac activation by either thrombin or collagen whereas protein kinase C inhibition was without effect. In contrast to Rac, Cdc42 activation was independent of phospholipase C activation, indicating that the two GTPases are differently regulated. We also found that phosphoinositide 3-kinase was not required for Rac activation in response to thrombin but was involved in its activation by collagen. ß

Rac regulates collagen-induced HSP27 phosphorylation via p44/p42 MAP kinase in human platelets

“…It has been reported that collagen stimulates Rac GTPase activation in human platelets and that Rac is essential for thrombus formation (12,13). We found that collagen marke dly increased the levels of GTP-Rac in human platelets in a time-dependent manner.…”

“…As regards Rac in platelets, it has been shown that platelets express the Rho family, including Rac (12). In addition, collagen and thrombin reportedly stimulate the activation of Rac, which is critical for thrombus formation (12,13). However, the exact role of Rac in human platelets has not yet been clarified.…”

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

“…In other cell systems, RhoG is known to activate Rac via interaction with ELMO and DOCK180 (21)(22)(23). Previous studies have shown that Rac1 is activated in platelets by a number of agonists (45)(46)(47) and plays an important role in aggregation, secretion, and clot retraction. Interestingly, Rac1 is known to be essential for the regulation of PLC␥2 in platelets downstream of GPVI or CLEC-2 (48,49).…”

Involvement of Rac in thromboxane A2-induced human platelet activation: Regulation of sCD40 ligand release and PDGF-AB secretion

“…With regard to Rac in platelets, it has been demonstrated that platelets express the Rho-family GTPases, including Rac (9). Additionally, in platelets, collagen and thrombin reportedly stimulate the activation of Rac, which is important in thrombus formation (9,10). However, the exact role of Rac in human platelets remains to be elucidated.…”