Kinase Family TAM

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Kinase Classification: Group TK: Family TAM

Vertebrate-specific family of receptor tyrosine kinases. This family was named "Axl" until 2016. TAM represents the three human members: Tyro3, Axl, and Mer

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Evolution

TAMs are found in all vertebrates, with likely orthologs in invertebrate chordates and possibly other invertebrates. There are three members in humans and other tetrapods and four in most fish. A possible TAM has been seen in the invertebrate chordate, Ciona intestinalis.

Domain Structure

TAMs are single-pass transmembrane proteins, with extracellular Ig and FN3 domains, and an intracellular tyrosine kinase domain.

Function

TAMs have overlapping functions. They all bind a pair of homologous ligands, protein S and Gas6. They lack embryonic developmental functions (even a triple knockout mouse is viable and fertile) and have homeostatic regulatory roles in several adult tissues [1].

TAMs activate canonical PI3K and Ras signaling pathway via Grb2 binding sites C-terminal of the kinase domain, and in immune cells also interact with interferon receptors and induce a JAK/STAT response.

References

  1. Lemke G. Biology of the TAM receptors. Cold Spring Harb Perspect Biol. 2013 Nov 1;5(11):a009076. DOI:10.1101/cshperspect.a009076 | PubMed ID:24186067 | HubMed [Lemke]