Human gene coding for the GAS6 protein
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.[ 5]
Interactions Gas6 has been shown to interact with AXL receptor tyrosine kinase , MerTK and TYRO3 .[ 6] [ 7]
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. The action of vitamin K is essential on GAS6 function.[ 8]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000183087 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031451 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Entrez Gene: GAS6 growth arrest-specific 6" .
^ Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (Apr 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 .
^ Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (Nov 1996). "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 .
^ Bellido-Martín L, de Frutos PG (2008). "Vitamin K-dependent actions of Gas6". Vitamins and Hormones . 78 : 185–209. doi :10.1016/S0083-6729(07)00009-X . hdl :10261/37140 . ISBN 978-0-12-374113-4 . PMID 18374195 .
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. Bibcode :1995Natur.373..623V . doi :10.1038/373623a0 . PMID 7854420 . S2CID 4242251 .
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. doi :10.1128/MCB.13.8.4976 . 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. doi :10.1523/JNEUROSCI.16-06-02012.1996 . PMC 6578513 . 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/art.1780400814 . 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. Bibcode :1997FEBSL.415...56M . 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. Bibcode :1997FEBSL.415...59G . 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 . S2CID 868501 .
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 . S2CID 10502090 .
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. doi :10.1523/JNEUROSCI.23-10-04208.2003 . PMC 6741089 . PMID 12764109 .