Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets

Joseph Aslan, Alex M. Spencer, Cassandra P. Loren, Jiaqing Pang, Heidi C. Welch, Daniel L. Greenberg, Owen McCarty

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Blood platelets undergo a carefully regulated change in shape to serve as the primary mediators of hemostasis and thrombosis. These processes manifest through platelet spreading and aggregation and are dependent on platelet actin cytoskeletal changes orchestrated by the Rho GTPase family member Rac1. To elucidate how Rac1 is regulated in platelets, we captured Rac1-interacting proteins from platelets and identified Rac1-associated proteins by mass spectrometry.Findings: Here, we demonstrate that Rac1 captures the Rac guanine nucleotide exchange factor P-Rex1 from platelet lysates. Western blotting experiments confirmed that P-Rex1 is expressed in platelets and associated with Rac1. To investigate the functional role of platelet P-Rex1, platelets from P-Rex1-/--deficient mice were treated with platelet agonists or exposed to platelet activating surfaces of fibrinogen, collagen and thrombin. Platelets from P-Rex1-/- mice responded to platelet agonists and activating surfaces similarly to wild type platelets.Conclusions: These findings suggest that P-Rex1 is not required for Rac1-mediated platelet activation and that the GEF activities of P-Rex1 may be more specific to GPCR chemokine receptor mediated processes in immune cells and tumor cells.

Original languageEnglish (US)
Article number11
JournalJournal of Molecular Signaling
Volume6
DOIs
StatePublished - Sep 1 2011

Fingerprint

Guanine Nucleotide Exchange Factors
Platelets
Blood Platelets
rac1 GTP-Binding Protein
rho GTP-Binding Proteins
Chemokine Receptors
Platelet Activation
Hemostasis
Platelet Aggregation
Thrombin
Fibrinogen
Actins

Keywords

  • Cytoskeletal remodeling
  • GEF
  • Platelet signaling
  • Small GTPase

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets. / Aslan, Joseph; Spencer, Alex M.; Loren, Cassandra P.; Pang, Jiaqing; Welch, Heidi C.; Greenberg, Daniel L.; McCarty, Owen.

In: Journal of Molecular Signaling, Vol. 6, 11, 01.09.2011.

Research output: Contribution to journalArticle

Aslan, Joseph ; Spencer, Alex M. ; Loren, Cassandra P. ; Pang, Jiaqing ; Welch, Heidi C. ; Greenberg, Daniel L. ; McCarty, Owen. / Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets. In: Journal of Molecular Signaling. 2011 ; Vol. 6.
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