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Stem cell factor receptor/c-Kit: from basic science to clinical implications

Lennartsson, Johan and Rönnstrand, Lars LU (2012) In Physiological Reviews 92(4). p.1619-1649
Abstract
Lennartsson J, Ronnstrand L. Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications. Physiol Rev 92: 1619-1649, 2012; doi: 10.1152/physrev.00046.2011.-Stem cell factor (SCF) is a dimeric molecule that exerts its biological functions by binding to and activating the receptor tyrosine kinase c-Kit. Activation of c-Kit leads to its autophosphorylation and initiation of signal transduction. Signaling proteins are recruited to activated c-Kit by certain interaction domains (e.g., SH2 and PTB) that specifically bind to phosphorylated tyrosine residues in the intracellular region of c-Kit. Activation of c-Kit signaling has been found to mediate cell survival, migration, and proliferation depending on the cell type. Signaling... (More)
Lennartsson J, Ronnstrand L. Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications. Physiol Rev 92: 1619-1649, 2012; doi: 10.1152/physrev.00046.2011.-Stem cell factor (SCF) is a dimeric molecule that exerts its biological functions by binding to and activating the receptor tyrosine kinase c-Kit. Activation of c-Kit leads to its autophosphorylation and initiation of signal transduction. Signaling proteins are recruited to activated c-Kit by certain interaction domains (e.g., SH2 and PTB) that specifically bind to phosphorylated tyrosine residues in the intracellular region of c-Kit. Activation of c-Kit signaling has been found to mediate cell survival, migration, and proliferation depending on the cell type. Signaling from c-Kit is crucial for normal hematopoiesis, pigmentation, fertility, gut movement, and some aspects of the nervous system. Deregulated c-Kit kinase activity has been found in a number of pathological conditions, including cancer and allergy. The observation that gain-of-function mutations in c-Kit can promote tumor formation and progression has stimulated the development of therapeutics agents targeting this receptor, e.g., the clinically used inhibitor imatinib mesylate. Also other clinically used multiselective kinase inhibitors, for instance, sorafenib and sunitinib, have c-Kit included in their range of targets. Furthermore, loss-of-function mutations in c-Kit have been observed and shown to give rise to a condition called piebaldism. This review provides a summary of our current knowledge regarding structural and functional aspects of c-Kit signaling both under normal and pathological conditions, as well as advances in the development of low-molecular-weight molecules inhibiting c-Kit function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physiological Reviews
volume
92
issue
4
pages
1619 - 1649
publisher
American Physiological Society
external identifiers
  • wos:000310055900004
  • scopus:84867718489
ISSN
1522-1210
DOI
10.1152/physrev.00046.2011
language
English
LU publication?
yes
id
5614bc10-e041-418a-bc22-e5c56436ad5e (old id 3287786)
date added to LUP
2013-01-07 09:44:22
date last changed
2017-11-19 03:08:50
@article{5614bc10-e041-418a-bc22-e5c56436ad5e,
  abstract     = {Lennartsson J, Ronnstrand L. Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications. Physiol Rev 92: 1619-1649, 2012; doi: 10.1152/physrev.00046.2011.-Stem cell factor (SCF) is a dimeric molecule that exerts its biological functions by binding to and activating the receptor tyrosine kinase c-Kit. Activation of c-Kit leads to its autophosphorylation and initiation of signal transduction. Signaling proteins are recruited to activated c-Kit by certain interaction domains (e.g., SH2 and PTB) that specifically bind to phosphorylated tyrosine residues in the intracellular region of c-Kit. Activation of c-Kit signaling has been found to mediate cell survival, migration, and proliferation depending on the cell type. Signaling from c-Kit is crucial for normal hematopoiesis, pigmentation, fertility, gut movement, and some aspects of the nervous system. Deregulated c-Kit kinase activity has been found in a number of pathological conditions, including cancer and allergy. The observation that gain-of-function mutations in c-Kit can promote tumor formation and progression has stimulated the development of therapeutics agents targeting this receptor, e.g., the clinically used inhibitor imatinib mesylate. Also other clinically used multiselective kinase inhibitors, for instance, sorafenib and sunitinib, have c-Kit included in their range of targets. Furthermore, loss-of-function mutations in c-Kit have been observed and shown to give rise to a condition called piebaldism. This review provides a summary of our current knowledge regarding structural and functional aspects of c-Kit signaling both under normal and pathological conditions, as well as advances in the development of low-molecular-weight molecules inhibiting c-Kit function.},
  author       = {Lennartsson, Johan and Rönnstrand, Lars},
  issn         = {1522-1210},
  language     = {eng},
  number       = {4},
  pages        = {1619--1649},
  publisher    = {American Physiological Society},
  series       = {Physiological Reviews},
  title        = {Stem cell factor receptor/c-Kit: from basic science to clinical implications},
  url          = {http://dx.doi.org/10.1152/physrev.00046.2011},
  volume       = {92},
  year         = {2012},
}