Growth arrest specific gene (GAS) 6 modulates platelet thrombus formation and vascular wall homeostasis and represents an attractive drug target

Andrew O. Maree, Hani Jneid, Igor F. Palacios, Kenneth Rosenfield, Calum A. MacRae, Desmond J. Fitzgerald

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

GAS6, the product of growth arrest specific (GAS) gene 6 is a ligand for the tyrosine protein kinase receptors Axl, Tyro3 and Mer whose signaling has been implicated in cell growth, survival, adhesion and migration. Although a secreted human vitamin K-dependent protein with close structural similarity with protein S, GAS6 does not exhibit anticoagulant properties but rather may be an important regulator of vascular homeostasis and platelet signaling. GAS6 signals via its receptor tyrosine kinases and appears to modulate platelet outside-in signaling via GP αIIbβ III, playing a key role in the perpetuation of platelet aggregates and clot retraction. GAS6 is also implicated in foam cell formation and neointimal proliferation in response to vascular injury. Thus GAS6 acts at key points in the pathophysiology of atherosclerosis and thrombosis; two processes implicated in most acute cardiovascular pathology. Inhibition of GAS6 or its receptors may provide antithrombotic activity in the absence of increased bleeding and thus presents an attractive drug target. GAS6 signaling may be modulated through direct antibody inhibition, blockade of its receptors or GAS6 tapping. However, ubiquitous expression of GAS6 and its receptors and the diverse biological effects of the pathway may make selective drug targeting difficult.

Original languageEnglish (US)
Pages (from-to)2656-2661
Number of pages6
JournalCurrent Pharmaceutical Design
Volume13
Issue number26
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • Early region 1A gene
  • Glycoprotein
  • Platelet response amplifier
  • Rreceptor tyrosine kinases
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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