Publication

GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.

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Last modified
  • 05/22/2025
Type of Material
Authors
    Luke A. Law, Mayo ClinicDoug Graham, Emory UniversityJorge Di Paola, University of ColoradoBrian R. Branchford, University of Colorado
Language
  • English
Date
  • 2018
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2018 Law, Graham, Di Paola and Branchford.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 2296-858X
Volume
  • 5
Start Page
  • 137
End Page
  • 137
Grant/Funding Information
  • DG has filed a patent application for use of MERTK inhibition as cancer therapy.
  • This study was supported in part by the National Hemophilia Foundation/Baxter Clinical Research Fellowship, American Society of Hematology Scholar Award, Hemostasis, and Thrombosis Research Society Mentored Research Award (HTRS-MRA), CSL Behring/Prof. Heimburger Award in Hemostasis, and NIH K12HD068372-03 Child Health Research Career Development grant (BB), NIH R01HL084086, R01HL120728 and the Postle Family Chair of Pediatric Cancer and Blood Disorders (JD), and 5H30MC00008-20-00 HRSA/MCHB (BB and JD).
Abstract
  • The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.
Author Notes
Keywords
Research Categories
  • Health Sciences, Oncology

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