The role of TAM family receptors and ligands in the nervous system: From development to pathobiology

Bridget Shafit-Zagardo, Ross C. Gruber, Juwen C. DuBois

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K–dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K–dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 −/− and TAM mutant mice models.

Original languageEnglish (US)
Pages (from-to)97-117
Number of pages21
JournalPharmacology and Therapeutics
StatePublished - Aug 2018


  • Axl and Mertk receptor tyrosine kinase family
  • Gas6
  • Homeostasis in the nervous system
  • Inflammation
  • Myelination
  • Phagocytosis
  • ProS1
  • Tyro3

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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