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Gas6 is complexed to soluble tyrosine kinase receptor Axl in human blood.

Ekman, Carl LU ; Stenhoff, Jonas LU and Dahlbäck, Björn LU (2010) In Journal of Thrombosis and Haemostasis 8(4). p.838-844
Abstract
Summary Background: The vitamin K-dependent Gas6 protein (product of growth arrest specific gene 6) binds to, and activates the TAM receptor tyrosine kinases Tyro3, Axl, and Mer. Gas6 and the TAM receptors have been suggested to be important for primary platelet functions, but Gas6 cannot be found in human platelets. However, Gas6 is present in human plasma at a concentration of around 0.2 nM, which is 1,000-fold lower than that of the homologous protein S. The Axl and Mer receptors can be cleaved close to the cell membrane, yielding soluble molecules consisting of the extracellular parts of the receptors. Objective: To investigate if soluble Axl (sAxl) is present in human serum and plasma and if Gas6 circulates in complex with sAxl.... (More)
Summary Background: The vitamin K-dependent Gas6 protein (product of growth arrest specific gene 6) binds to, and activates the TAM receptor tyrosine kinases Tyro3, Axl, and Mer. Gas6 and the TAM receptors have been suggested to be important for primary platelet functions, but Gas6 cannot be found in human platelets. However, Gas6 is present in human plasma at a concentration of around 0.2 nM, which is 1,000-fold lower than that of the homologous protein S. The Axl and Mer receptors can be cleaved close to the cell membrane, yielding soluble molecules consisting of the extracellular parts of the receptors. Objective: To investigate if soluble Axl (sAxl) is present in human serum and plasma and if Gas6 circulates in complex with sAxl. Methods: We expressed recombinant sAxl, raised antibodies, developed and validated an ELISA for Axl. Serum and plasma were analyzed using ELISAs for Gas6, Axl, and sAxl-Gas6 complexes. Serum was gel filtered and fractions analyzed by the different ELISAs to determine if Gas6 in serum is free or complexed. Immunoprecipitation was used to investigate binding between Gas6 and sAxl in serum. Results: sAxl is present in serum and plasma at around 0.6 nM and all Gas6 is bound to sAxl. No complexes between Gas6 and the soluble forms of Mer and Tyro3 could be detected, indicating that sAxl is the physiological binder of Gas6 in human serum. Conclusions: Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gas6, Axl, receptor tyrosine kinase, TAM
in
Journal of Thrombosis and Haemostasis
volume
8
issue
4
pages
838 - 844
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000275922500030
  • pmid:20088931
  • scopus:77952683864
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2010.03752.x
language
English
LU publication?
yes
id
d32e9c9c-4a05-4661-b4c9-3baff4657838 (old id 1540765)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20088931?dopt=Abstract
date added to LUP
2010-02-03 10:52:01
date last changed
2018-06-24 03:35:05
@article{d32e9c9c-4a05-4661-b4c9-3baff4657838,
  abstract     = {Summary Background: The vitamin K-dependent Gas6 protein (product of growth arrest specific gene 6) binds to, and activates the TAM receptor tyrosine kinases Tyro3, Axl, and Mer. Gas6 and the TAM receptors have been suggested to be important for primary platelet functions, but Gas6 cannot be found in human platelets. However, Gas6 is present in human plasma at a concentration of around 0.2 nM, which is 1,000-fold lower than that of the homologous protein S. The Axl and Mer receptors can be cleaved close to the cell membrane, yielding soluble molecules consisting of the extracellular parts of the receptors. Objective: To investigate if soluble Axl (sAxl) is present in human serum and plasma and if Gas6 circulates in complex with sAxl. Methods: We expressed recombinant sAxl, raised antibodies, developed and validated an ELISA for Axl. Serum and plasma were analyzed using ELISAs for Gas6, Axl, and sAxl-Gas6 complexes. Serum was gel filtered and fractions analyzed by the different ELISAs to determine if Gas6 in serum is free or complexed. Immunoprecipitation was used to investigate binding between Gas6 and sAxl in serum. Results: sAxl is present in serum and plasma at around 0.6 nM and all Gas6 is bound to sAxl. No complexes between Gas6 and the soluble forms of Mer and Tyro3 could be detected, indicating that sAxl is the physiological binder of Gas6 in human serum. Conclusions: Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors.},
  author       = {Ekman, Carl and Stenhoff, Jonas and Dahlbäck, Björn},
  issn         = {1538-7933},
  keyword      = {Gas6,Axl,receptor tyrosine kinase,TAM},
  language     = {eng},
  number       = {4},
  pages        = {838--844},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Gas6 is complexed to soluble tyrosine kinase receptor Axl in human blood.},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2010.03752.x},
  volume       = {8},
  year         = {2010},
}