JBC Focus on PI3-Kinase with Echelon

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on March 7, 2003
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
278/11/9159    most recent
M211726200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Voytyuk, O.
Right arrow Articles by Rönnstrand, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Voytyuk, O.
Right arrow Articles by Rönnstrand, L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print January 2, 2003
J. Biol. Chem, 10.1074/jbc.M211726200
Submitted on November 18, 2002
Revised on December 19, 2002
Accepted on January 2, 2003

Src family kinases are involved in the differential signaling from two splice-forms of c-Kit

Olexandr Voytyuk, Johan Lennartsson, Akira Mogi, Georgina Caruana, Sara Courtneidge, Leonie K. Ashman, and Lars Rönnstrand

Experimental Clinical Chemistry, Lund University, Wallenberg Laboratory, Malmö University Hospital, Malmö, Sweden 20502

Corresponding Author: Lars.Ronnstrand{at}klkemi.mas.lu.se

In both mice and humans alternate splicing results in isoforms of c-Kit characterized by the presence or the absence of a tetrapeptide sequence, GNNK, in the juxtamembrane region of the extracellular domain. Dramatic differences in the kinetics and magnitude of activation of the intrinsic tyrosine kinase activity of c-Kit between the GNNK- and GNNK+ isoforms has previously been shown. Here we report the analysis of downstream targets of receptor signaling, which revealed that the signaling was differentially regulated in the two splice-forms. The kinetics of phosphorylation of Shc, previously demonstrated to be phosphorylated by Src downstream of c-Kit, was stronger and more rapid in the GNNK- form, while it showed slower kinetics in the GNNK+ form. Inhibition of Src family kinases with the specific Src family kinase inhibitor SU6656 altered the kinetics of activation of the GNNK- form of c-Kit so that it resembled that of the GNNK+ form. In cells expressing the GNNK- form, SCF was rapidly degraded, while in cells expressing the GNNK+ form only showed a very slow rate of degradation of SCF. In the GNNK+ form the Src inhibitor SU6656 only had a weak effect on degradation, while in the GNNK- form it dramatically inhibited degradation. In summary, the two splice forms show, despite only four amino acid sequence difference, remarkable differences in their signaling capabilities.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. Sun, M. Pedersen, and L. Ronnstrand
Gab2 Is Involved in Differential Phosphoinositide 3-Kinase Signaling by Two Splice Forms of c-Kit
J. Biol. Chem., October 10, 2008; 283(41): 27444 - 27451.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
J. C. Montero, R. Lopez-Perez, J. F. San Miguel, and A. Pandiella
Expression of c-Kit isoforms in multiple myeloma: differences in signaling and drug sensitivity
Haematologica, June 1, 2008; 93(6): 851 - 859.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Jahn, S. Sindhu, S. Gooch, P. Seipel, P. Lavori, E. Leifheit, and K. Weinberg
Direct interaction between Kit and the interleukin-7 receptor
Blood, September 15, 2007; 110(6): 1840 - 1847.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
L. Liu, S. Rajareddy, P. Reddy, K. Jagarlamudi, C. Du, Y. Shen, Y. Guo, K. Boman, E. Lundin, U. Ottander, et al.
Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development
J. Mol. Endocrinol., January 1, 2007; 38(1): 137 - 146.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Heiss, K. Masson, C. Sundberg, M. Pedersen, J. Sun, S. Bengtsson, and L. Ronnstrand
Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2
Blood, September 1, 2006; 108(5): 1542 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
K.J. Hutt, E.A. McLaughlin, and M.K. Holland
Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis
Mol. Hum. Reprod., February 1, 2006; 12(2): 61 - 69.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. Lennartsson, T. Jelacic, D. Linnekin, and R. Shivakrupa
Normal and Oncogenic Forms of the Receptor Tyrosine Kinase Kit
Stem Cells, January 1, 2005; 23(1): 16 - 43.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Kindler, F. Breitenbuecher, A. Marx, J. Beck, G. Hess, B. Weinkauf, J. Duyster, C. Peschel, C. J. Kirkpatrick, M. Theobald, et al.
Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia
Blood, May 15, 2004; 103(10): 3644 - 3654.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.