2017
DOI: 10.3389/fimmu.2017.01521
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Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6

Abstract: The Tyro3, Axl, and Mertk (TAM) receptors are homologous type I receptor tyrosine kinases that have critical functions in the clearance of apoptotic cells in multicellular organisms. TAMs are activated by their endogenous ligands, growth arrest-specific 6 (Gas6), and protein S (Pros1), that function as bridging molecules between externalized phosphatidylserine (PS) on apoptotic cells and the TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote TAM activation remains elusive. Using TAM… Show more

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Cited by 65 publications
(48 citation statements)
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“…VK‐mediated gamma‐glutamyl carboxylation of Gas6 (cGas6) shows the highest affinity binding with AXL, a member of the TAM receptor tyrosine kinase protein family . The binding of cGas6 with AXL causes the tyrosine phosphorylation of AXL, followed by the activation of PI3K .…”
Section: Discussionmentioning
confidence: 99%
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“…VK‐mediated gamma‐glutamyl carboxylation of Gas6 (cGas6) shows the highest affinity binding with AXL, a member of the TAM receptor tyrosine kinase protein family . The binding of cGas6 with AXL causes the tyrosine phosphorylation of AXL, followed by the activation of PI3K .…”
Section: Discussionmentioning
confidence: 99%
“…VK-mediated gamma-glutamyl carboxylation of Gas6 (cGas6) shows the highest affinity binding with AXL, a member of the TAM receptor tyrosine kinase protein family. 8,10 The binding of cGas6 with AXL causes the tyrosine phosphorylation of AXL, followed by the activation of PI3K. 6,7 After the activation, PI3K stimulates the formation of PIP3, which causes the phosphorylation of PKB (or AKT), followed by GLUT4 translocation from the intracellular pool to the plasma membrane and glucose uptake.…”
Section: Discussionmentioning
confidence: 99%
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“…Up until recently protein S was thought to exclusively be a ligand for TYRO3 and MER, but recently it has been shown to be capable of binding to and activating AXL in glioblastoma cells [9]. Activation of AXL is not complete until a further interaction with the phospholipid phosphatidyl serine (PS) occurs, mediated by the gamma-carboxyglutamic acid (Gla) domain on GAS6 following its posttranslational modification [10]. PS is a phospholipid that is normally restricted to the intracellular portion of the phospholipid bilayer but is externalized in apoptotic cells or cells that are otherwise stressed, such as in virally infected cells.…”
Section: Axl Signaling Axismentioning
confidence: 99%