Integrin αIIbβ3-mediated translocation of CDC42Hs to the Cytoskeleton in Stimulated Human Platelets

Dash, Debabrata ; Aepfelbacher, Martin ; Siess, Wolfgang (1995) Integrin αIIbβ3-mediated translocation of CDC42Hs to the Cytoskeleton in Stimulated Human Platelets Journal of Biological Chemistry, 270 (29). pp. 17321-17326. ISSN 0021-9258

PDF - Other

Official URL:

Related URL:


To investigate the function of the human Ras-related CDC42 GTP-binding protein (CDC42Hs) we studied its subcellular redistribution in platelets stimulated by thrombin-receptor activating peptide (TRAP) or ADP. In resting platelets CDC42Hs was detected exclusively in the membrane skeleton (9.6 ± 1.5% of total) and the detergent soluble fraction (90 ± 4%). When platelets were aggregated with TRAP or ADP, CDC42Hs (10% of total) appeared in the cytoskeleton and decreased in the membrane skeleton, whereas RhoGDI (guanine-nucleotide dissociation inhibitor) and CDC42HsGAP (GTPase-activating protein) remained exclusively in the detergent-soluble fraction. Upon prolonged platelet stimulation CDC42Hs disappeared from the cytoskeleton and reappeared in the membrane skeleton. Rac translocated to the cytoskeleton with a similar time course as CDC42Hs. When platelets were stimulated under conditions that precluded the activation of the αIIbβ3 integrin and platelet aggregation, cytoskeletal association of CDC42Hs was abolished. Translocation of CDC42Hs to the cytoskeleton but not aggregation was also prevented by cytochalasins B or D or the protein tyrosine kinase inhibitor genistein. Platelet secretion and thromboxane formation were not required but facilitated the cytoskeletal association of CDC42Hs. The results indicate that in platelets stimulated by TRAP or ADP, a fraction of CDC42Hs translocates from the membrane skeleton to the cytoskeleton. This process is reversible and is mediated by activation of the αIIbβ3 integrin and subsequent actin polymerization and protein-tyrosine kinase stimulation. CDC42Hs might be a new component of a signaling complex containing specific cytoskeletal proteins and protein-tyrosine kinases that forms after activation of the αIIbβ3 integrin in platelets.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
ID Code:101340
Deposited On:04 Feb 2017 17:17
Last Modified:04 Feb 2017 17:17

Repository Staff Only: item control page