Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications

Johan Lennartsson; Lars Rönnstrand

doi:10.1152/physrev.00046.2011

journal article Oct 01, 2012

Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications

Johan Lennartsson Lars Rönnstrand

Physiological Reviews Vol. 92 No. 4 pp. 1619-1649 · American Physiological Society

View at Publisher Save 10.1152/physrev.00046.2011

Abstract

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.

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Details

Published: Oct 01, 2012
Vol/Issue: 92(4)
Pages: 1619-1649

Authors

J

Johan Lennartsson

Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden; and Experimental Clinical Chemistry, Wallenberg Laboratory, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden

L

Lars Rönnstrand

Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden; and Experimental Clinical Chemistry, Wallenberg Laboratory, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden

Cite This Article

Johan Lennartsson, Lars Rönnstrand (2012). Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications. Physiological Reviews, 92(4), 1619-1649. https://doi.org/10.1152/physrev.00046.2011

Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications

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