GAS6

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Species	Human	Mouse
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View/Edit Human

Growth arrest-specific 6, also known as GAS6, is a human gene coding for the Gas6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth arrested fibroblasts.

Function

Gas6 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation.

Interactions

Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3.

The presence of Gla needs a vitamin K-dependent enzymatic reaction that carboxylates the gamma carbon of certain glutamic residues of the protein during its production in the endoplasmic reticulum.

Further reading

• Maree AO, Jneid H, Palacios IF, Rosenfield K, MacRae CA, Fitzgerald DJ (2007). "Growth arrest specific gene (GAS) 6 modulates platelet thrombus formation and vascular wall homeostasis and represents an attractive drug target". Curr. Pharm. Des. 13 (26): 2656–61. doi:10.2174/138161207781662948. PMID 17897008.
• Varnum BC, Young C, Elliott G, Garcia A, Bartley TD, Fridell YW, Hunt RW, Trail G, Clogston C, Toso RJ (1995). "Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6". Nature. 373 (6515): 623–6. doi:10.1038/373623a0. PMID 7854420.
• Stitt TN, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies DR, Jones PF (1995). "The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases". Cell. 80 (4): 661–70. doi:10.1016/0092-8674(95)90520-0. PMID 7867073.
• Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993). "The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade". Mol. Cell. Biol. 13 (8): 4976–85. PMC 360142. PMID 8336730.
• Saccone S, Marcandalli P, Gostissa M, Schneider C, Della Valle G (1996). "Assignment of the human GAS6 gene to chromosome 13q34 by fluorescence in situ hybridization". Genomics. 30 (1): 129–31. doi:10.1006/geno.1995.0027. PMID 8595896.
• Li R, Chen J, Hammonds G, Phillips H, Armanini M, Wood P, Bunge R, Godowski PJ, Sliwkowski MX, Mather JP (1996). "Identification of Gas6 as a growth factor for human Schwann cells". J. Neurosci. 16 (6): 2012–9. PMID 8604045.
• Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (1996). "Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl". J. Biol. Chem. 271 (16): 9785–9. doi:10.1074/jbc.271.16.9785. PMID 8621659.
• Goruppi S, Ruaro E, Schneider C (1996). "Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts". Oncogene. 12 (3): 471–80. PMID 8637702.
• Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1997). "Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases". J. Biol. Chem. 271 (47): 30022–7. doi:10.1074/jbc.271.47.30022. PMID 8939948.
• Loeser RF, Varnum BC, Carlson CS, Goldring MB, Liu ET, Sadiev S, Kute TE, Wallin R (1997). "Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor axl: potential role in autocrine signaling in cartilage". Arthritis Rheum. 40 (8): 1455–65. doi:10.1002/1529-0131(199708)40:8<1455::AID-ART14>3.0.CO;2-B. PMID 9259426.
• Marcandalli P, Gostissa M, Varnum B, Goruppi S, Schneider C (1997). "Identification and tissue expression of a splice variant for the growth arrest-specific gene gas6". FEBS Lett. 415 (1): 56–8. doi:10.1016/S0014-5793(97)01094-6. PMID 9326368.
• Goruppi S, Yamane H, Marcandalli P, Garcia A, Clogston C, Gostissa M, Varnum B, Schneider C (1997). "The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation". FEBS Lett. 415 (1): 59–63. doi:10.1016/S0014-5793(97)01093-4. PMID 9326369.
• Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, Nagata K, Ohashi K, Mizuno K, Arita H (1997). "Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6". J. Biol. Chem. 272 (47): 29411–4. doi:10.1074/jbc.272.47.29411. PMID 9367994.
• Prieto AL, Weber JL, Lai C (2000). "Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system". J. Comp. Neurol. 425 (2): 295–314. doi:10.1002/1096-9861(20000918)425:2<295::AID-CNE11>3.0.CO;2-G. PMID 10954847.
• Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlbäck B, Carmeliet P (2001). "Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis". Nat. Med. 7 (2): 215–21. doi:10.1038/84667. PMID 11175853.
• Sun WS, Misao R, Iwagaki S, Fujimoto J, Tamaya T (2003). "Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis". Mol. Hum. Reprod. 8 (6): 552–8. doi:10.1093/molehr/8.6.552. PMID 12029073.
• Sasaki T, Knyazev PG, Cheburkin Y, Göhring W, Tisi D, Ullrich A, Timpl R, Hohenester E (2003). "Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains". J. Biol. Chem. 277 (46): 44164–70. doi:10.1074/jbc.M207340200. PMID 12218057.
• Ito M, Nakashima M, Nakayama T, Ohtsuru A, Nagayama Y, Takamura N, Demedchik EP, Sekine I, Yamashita S (2003). "Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl". Thyroid. 12 (11): 971–5. doi:10.1089/105072502320908303. PMID 12490074.
• Shankar SL, O'Guin K, Cammer M, McMorris FA, Stitt TN, Basch RS, Varnum B, Shafit-Zagardo B (2003). "The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway". J. Neurosci. 23 (10): 4208–18. PMID 12764109.