Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 49-56 ◽  
Author(s):  
T. Hirata ◽  
E. Morii ◽  
M. Morimoto ◽  
T. Kasugai ◽  
T. Tsujimura ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Dorsal Root ◽  
Mouse Embryos ◽  
Kit Receptor ◽  
Vitro Effect

The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.

Transdifferentiation of pancreatic acinar cells, and the role of stem cell factor and c-kit receptor tyrosine kinase signal transduction system

Pancreatology ◽  
2013 ◽  
Vol 13 (2) ◽  
pp. e71
Author(s):  
M. Satake ◽  
G. Eibl ◽  
T. Hamada ◽  
H. Ishikawa ◽  
V.L. Go ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Signal Transduction System ◽  
Kit Receptor

PANCREAS-TRANSDIFFERENTIATION INDUCED BY SIGNAL TRANSDUCTION SYSTEM OF STEM CELL FACTOR AND C-KIT RECEPTOR TYROSINE KINASE

Pancreas ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 493
Author(s):  
M. Satake ◽  
G. Eibl ◽  
K. Suzumura ◽  
T. Hirano ◽  
T. Okada ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Signal Transduction System ◽  
Kit Receptor

S1886 Pancreatic Transdifferentiation Induced By Signal Transduction System of c-Kit Receptor Tyrosine Kinase and Its Ligand Stem Cell Factor

2008 ◽  
Vol 134 (4) ◽  
pp. A-287
Author(s):  
Makoto Satake ◽  
Tetsuhiro Hamada ◽  
Guido Eibl ◽  
Kazuhiro Suzumura ◽  
Tadamichi Hirano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Signal Transduction System ◽  
Kit Receptor

scholarly journals A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

Diabetologia ◽  
2015 ◽  
Vol 58 (4) ◽  
pp. 654-665 ◽  
Author(s):  
Zhi-Chao Feng ◽  
Matthew Riopel ◽  
Alex Popell ◽  
Rennian Wang
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Beta Cells ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Pancreatic Beta Cells ◽  
Kit Receptor

Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl)

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 226-232 ◽  
Author(s):  
Shan Zeng ◽  
Zhiheng Xu ◽  
Stan Lipkowitz ◽  
Jack B. Longley
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Feedback Loop ◽  
Ring Finger ◽  
Negative Feedback Loop ◽  
E3 Ligases ◽  
Kit Receptor ◽  
Cbl Proteins

Abstract Activation of the KIT receptor tyrosine kinase contributes to the pathogenesis of several human diseases, but the mechanisms regulating KIT signaling have not been fully characterized. Here, we show that stem cell factor (SCF), the ligand for KIT, induces the interaction between KIT and Cbl proteins and their mutual degradation. Upon SCF stimulation, KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. We propose a negative feedback loop controlling the SCF-KIT signaling pathway, in which SCF activates KIT. The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. (Blood. 2005;105:226-232)

JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3688-3693 ◽  
Author(s):  
SR Weiler ◽  
S Mou ◽  
CS DeBerry ◽  
JR Keller ◽  
FW Ruscetti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Phosphorylation ◽  
Receptor Tyrosine Kinase ◽  
Antisense Oligonucleotides ◽  
Stem Cell Factor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Kinase C ◽  
Kit Receptor ◽  
Normal Human

Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF- stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway.

Expression of c-Kit receptor tyrosine kinase and effect on β-cell development in the human fetal pancreas

2007 ◽  
Vol 293 (2) ◽  
pp. E475-E483 ◽  
Author(s):  
Jinming Li ◽  
Jaclyn Quirt ◽  
Hung Quoc Do ◽  
Kristina Lyte ◽  
Fraser Fellows ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Differentiation ◽  
Β Cell ◽  
Hematopoietic Stem ◽  
Insulin Expression ◽  
Kit Receptor

The receptor, c-Kit, and its ligand, stem cell factor (SCF), are critical for hematopoietic stem cell differentiation and have been implicated in the development, function, and survival of rodent islets. Previously, we reported that exogenous SCF treatments of cultured human fetal (14–16 wk fetal age) islet-epithelial clusters enhanced islet cell differentiation and proliferation (Li J, Goodyer CG, Fellows F, Wang R. Int J Biochem Cell Biol 38: 961–972, 2006). In the present study, we examined the expression pattern of c-Kit in early to midgestation human fetal pancreata and the relevance of c-Kit receptor tyrosine kinase for insulin gene expression and β-cell survival. c-Kit is expressed in the intact pancreas in a cell-specific manner, with a significant decrease in immunoreactivity in the duct regions from 8 to 21 wk fetal age, paralleled by a significant increase in expression within endocrine regions. These c-Kit-positive cells are highly proliferative and show frequent coexpression with insulin and glucagon. Treatment of islet-epithelial clusters with anti-ACK45 antibody stimulates c-Kit phosphorylation paralleled by a significant increase in PDX-1 and insulin expression, increased cell proliferation, and reduced β-cell death. In contrast, transient transfection with c-Kit siRNA results in a three- to fourfold decrease in c-Kit, PDX-1, and insulin expression and decreased cell proliferation. This study describes important changes in the distribution and dynamics of c-Kit-expressing cells during human fetal pancreatic neogenesis, suggesting that c-Kit may be a marker for human pancreatic islet progenitor cells. Functional analysis of the c-Kit receptor tyrosine kinase provides evidence that phosphorylation of c-Kit receptor may be involved in mediating early β-cell differentiation and survival.

scholarly journals Signaling Through the Interaction of Membrane-Restricted Stem Cell Factor and c-kit Receptor Tyrosine Kinase: Genetic Evidence for a Differential Role in Erythropoiesis

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 879-889 ◽  
Author(s):  
Reuben Kapur ◽  
Manus Majumdar ◽  
Xiangli Xiao ◽  
Monica McAndrews-Hill ◽  
Karen Schindler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stromal Cells ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Erythropoietin Receptor ◽  
Soluble Form

Abstract Mutations of the receptor tyrosine kinase c-kit or its ligand stem cell factor (SCF), which is encoded as a soluble and membrane-associated protein by the Steel gene in mice, lead to deficiencies of germ cells, melanocytes, and hematopoiesis, including the erythroid lineage. In the present study, we have used genetic methods to study the role of membrane or soluble presentation of SCF in hematopoiesis. Bone marrow–derived stromal cells expressing only a membrane-restricted (MR) isoform of SCF induced an elevated and sustained tyrosine phosphorylation of both c-kit and erythropoietin receptor (EPO-R) and significantly greater proliferation of an erythrocytic progenitor cell line compared with stromal cells expressing soluble SCF. Transgene expression of MR-SCF inSteel-dickie (Sld) mutants resulted in a significant improvement in the production of red blood cells, bone marrow hypoplasia, and runting. In contrast, overexpression of the full-length soluble form of SCF transgene had no effect on either red blood cell production or runting but corrected the myeloid progenitor cell deficiency seen in these mutants. These data provide the first evidence of differential functions of SCF isoforms in vivo and suggest an abnormal signaling mechanism as the cause of the severe anemia seen in mutants of the Sl gene.

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