Advanced

The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases.

Hafizi, Sassan LU ; Gustafsson, Anna LU ; Stenhoff, Jonas LU and Dahlbäck, Björn LU (2005) In International Journal of Biochemistry & Cell Biology 37(Jun 16). p.2344-2356
Abstract
Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases, the biological ligand for which is the growth/survival factor Gas6. However, little is known about the molecular mechanisms for Axl activation and signal transduction. We have previously identified a novel interaction between the intracellular domain of Axl and Ran binding protein in microtubule organising centre (RanBPM). In the present study, we investigated further the nature of the RanBPM interaction with Axl. A wide distribution of RanBPM mRNA expression in human tissues and various human cancer cell lines was detected. The strength of interaction of both proteins in yeast was comparable to that with the other Axl-binding proteins phosphatidylinositol... (More)
Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases, the biological ligand for which is the growth/survival factor Gas6. However, little is known about the molecular mechanisms for Axl activation and signal transduction. We have previously identified a novel interaction between the intracellular domain of Axl and Ran binding protein in microtubule organising centre (RanBPM). In the present study, we investigated further the nature of the RanBPM interaction with Axl. A wide distribution of RanBPM mRNA expression in human tissues and various human cancer cell lines was detected. The strength of interaction of both proteins in yeast was comparable to that with the other Axl-binding proteins phosphatidylinositol 3-kinase and Grb2. A truncated version of RanBPM with the SPRY-LisH domain region omitted failed to interact with Axl in yeast. RanBPM was also found to interact in yeast with the Axl homologue, Sky/Tyro3. The interaction between Axl intracellular domain and RanBPM was reproduced in coimmunoprecipitation experiments in both cell-free and mammalian cell systems. Furthermore, coimmunoprecipitation revealed endogenous Axl and RanBPM to interact in several mammalian cell lines in a constitutive manner. Stimulation of COS cells with Gas6 caused increased Axl tyrosine phosphorylation although appeared not to influence the RanBPM-Axl association. In conclusion, we have identified and characterised a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. This novel insight into the signalling interactions of Axl and Sky may shed further light on their suspected roles in tumourigenesis, inflammation as well as other cell proliferative diseases. (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
Ran binding protein, Ax1, receptor tyrosine kinase, transduction, signal, Gas6
in
International Journal of Biochemistry & Cell Biology
volume
37
issue
Jun 16
pages
2344 - 2356
publisher
Elsevier
external identifiers
  • wos:000232238800011
  • pmid:15964779
  • scopus:23944496040
ISSN
1878-5875
DOI
10.1016/j.biocel.2005.05.006
language
English
LU publication?
yes
id
4d607cb0-5a52-47bc-a9e8-49718545cb46 (old id 139937)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15964779&query_hl=17
date added to LUP
2007-07-25 10:37:11
date last changed
2017-01-15 04:18:49
@article{4d607cb0-5a52-47bc-a9e8-49718545cb46,
  abstract     = {Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases, the biological ligand for which is the growth/survival factor Gas6. However, little is known about the molecular mechanisms for Axl activation and signal transduction. We have previously identified a novel interaction between the intracellular domain of Axl and Ran binding protein in microtubule organising centre (RanBPM). In the present study, we investigated further the nature of the RanBPM interaction with Axl. A wide distribution of RanBPM mRNA expression in human tissues and various human cancer cell lines was detected. The strength of interaction of both proteins in yeast was comparable to that with the other Axl-binding proteins phosphatidylinositol 3-kinase and Grb2. A truncated version of RanBPM with the SPRY-LisH domain region omitted failed to interact with Axl in yeast. RanBPM was also found to interact in yeast with the Axl homologue, Sky/Tyro3. The interaction between Axl intracellular domain and RanBPM was reproduced in coimmunoprecipitation experiments in both cell-free and mammalian cell systems. Furthermore, coimmunoprecipitation revealed endogenous Axl and RanBPM to interact in several mammalian cell lines in a constitutive manner. Stimulation of COS cells with Gas6 caused increased Axl tyrosine phosphorylation although appeared not to influence the RanBPM-Axl association. In conclusion, we have identified and characterised a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. This novel insight into the signalling interactions of Axl and Sky may shed further light on their suspected roles in tumourigenesis, inflammation as well as other cell proliferative diseases.},
  author       = {Hafizi, Sassan and Gustafsson, Anna and Stenhoff, Jonas and Dahlbäck, Björn},
  issn         = {1878-5875},
  keyword      = {Ran binding protein,Ax1,receptor tyrosine kinase,transduction,signal,Gas6},
  language     = {eng},
  number       = {Jun 16},
  pages        = {2344--2356},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry & Cell Biology},
  title        = {The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2005.05.006},
  volume       = {37},
  year         = {2005},
}