Activation of the Small GTPase Ral in Platelets

AUTOR(ES)

Wolthuis, Rob M. F.

FONTE

American Society for Microbiology

RESUMO

Ral is a ubiquitously expressed Ras-like small GTPase which is abundantly present in human platelets. The biological function of Ral and the signaling pathway in which Ral is involved are largely unknown. Here we describe a novel method to measure Ral activation utilizing the Ral binding domain of the putative Ral effector RLIP76 as an activation-specific probe. With this assay we investigated the signaling pathway that leads to Ral activation in human platelets. We found that Ral is rapidly activated after stimulation with various platelet agonists, including α-thrombin. In contrast, the platelet antagonist prostaglandin I2 inhibited α-thrombin-induced Ral activation. Activation of Ral by α-thrombin could be inhibited by depletion of intracellular Ca2+, whereas the induction of intracellular Ca2+ resulted in the activation of Ral. Our results show that Ral can be activated by extracellular stimuli. Furthermore, we show that increased levels of intracellular Ca2+ are sufficient for Ral activation in platelets. This activation mechanism correlates with the activation mechanism of the small GTPase Rap1, a putative upstream regulator of Ral guanine nucleotide exchange factors.

Documentos Relacionados

• FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK
• The small GTPase RalA targets filamin to induce filopodia
• Sequential Regulation of the Small GTPase Rap1 in Human Platelets
• Ral-GTPase Influences the Regulation of the Readily Releasable Pool of Synaptic Vesicles
• Activation of the Small GTPase Rac Is Sufficient to Disrupt Cadherin-dependent Cell-Cell Adhesion in Normal Human Keratinocytes