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J Thromb Haemost. 2018 Jun 08; doi: 10.1111/jth.14197. Epub 2018 Jun 08.

TC21/RRas2 regulates glycoprotein VI-FcRγ-mediated platelet activation and thrombus stability.

Journal of thrombosis and haemostasis : JTH

S Janapati, J Wurtzel, C Dangelmaier, B K Manne, D Bhavanasi, J C Kostyak, S Kim, M Holinstat, S P Kunapuli, L E Goldfinger

Affiliations

  1. The Sol Sherry Thrombosis Research Center and Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  2. The Sol Sherry Thrombosis Research Center and Department of Anatomy & Cell Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  3. Department of Pharmacology, Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  4. Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

PMID: 29883056 PMCID: PMC6286703 DOI: 10.1111/jth.14197

Abstract

Essentials RAS proteins are expressed in platelets but their functions are largely uncharacterized. TC21/RRas2 is required for glycoprotein VI-induced platelet responses and for thrombus stability in vivo. TC21 regulates platelet aggregation by control of α

SUMMARY: Background Many RAS family small GTPases are expressed in platelets, including RAC, RHOA, RAP, and HRAS/NRAS/RRAS1, but most of their signaling and cellular functions remain poorly understood. Like RRAS1, TC21/RRAS2 reverses HRAS-induced suppression of integrin activation in CHO cells. However, a role for TC21 in platelets has not been explored. Objectives To determine TC21 expression in platelets, TC21 activation in response to platelet agonists, and roles of TC21 in platelet function in in vitro and in vivo thrombosis. Results We demonstrate that TC21 is expressed in human and murine platelets, and is activated in response to agonists for the glycoprotein (GP) VI-FcRγ immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor, in an Src-dependent manner. GPVI-induced platelet aggregation, integrin α

© 2018 International Society on Thrombosis and Haemostasis.

Keywords: RAS proteins; blood platelets; collagen receptors; embolism and thrombosis; monomeric GTP-binding proteins

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