Reactome | MERTK receptor binds ligands (Gas6 or Protein S)

MERTK receptor binds ligands (Gas6 or Protein S)

Stable Identifier

R-HSA-202710

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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MERTK receptor binds ligands (Gas6 or Protein S)

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MerTK appears to be required for ingestion of apoptotic cells by professional phagocytes such as monocytes/macrophages, retinal pigment epithelial cells and dendritic cells. Mer appears to be able to induce the cytoskeletal remodelling that is required for engulfment during phagocytosis. For instance, a deletion in the MERTK gene was identified as the underlying cause for retinal dystrophy which involves an impairment in the ingestion of shed photoreceptor cell fragments by retinal pigment epithelial cells.

The biological ligands for MerTK are two highly similar vitamin K-dependent proteins, Gas6 and protein S (PS), a negative regulator of blood coagulation. Both proteins are composed an N-terminal region containing multiple post-translationally modified gamma-carboxyglutamic acid residues (Gla). The Gla region possesses the ability to interact in a conformationally specific manner with negatively charged membrane phospholipids, which is thought to mediate the binding of both Gas6 and PS to apoptotic cells. In this way, they are thought to act as recognition bridges between apoptotic cells and the phagocyte cell that ingest them.

Literature References

PubMed ID	Title	Journal	Year
16737840	Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases Hafizi, S, Dahlback, B	Cytokine Growth Factor Rev	2006
17442946	Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells Lemke, G, Earp, HS, Matsushima, GK, Camenisch, TD, Seitz, HM	J Immunol	2007
17064312	Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. Hafizi, S, Dahlback, B	FEBS J	2006