|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 December 2000, Vol. 96, No. 12, pp. 3734-3742
HEMATOPOIESIS
Differential stimulation of c-Kit mutants by membrane-bound and
soluble Steel Factor correlates with leukemic potential
Jennifer L. Gommerman,
Dino Sittaro,
Nadia Z. Klebasz,
David A. Williams, and
Stuart A. Berger
From The Arthritis and Immune Disorder Research Centre,
The Toronto Hospital and Department of Immunology, University of
Toronto, Toronto, Ontario, Canada; Department of Pediatrics, Herman B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for
Children, Howard Hughes Medical Institute, Indiana University
School of Medicine, Indianapolis, IN.
The authors investigated the roles of PI3-kinase and PLC-
in stimulation by Steel Factor (SLF) through c-Kit. c-Kit mutants YF719, YF728, and a YF719/YF728 double mutant were expressed in 32D
myelomonocytic cells. KitYF719 fails to recruit PI3-kinase after
stimulation with SLF, whereas KitYF728 fails to stimulate PLC-
phosphorylation or mobilize Ca++. Both single mutants
responded mitogenically to soluble SLF (sSLF) in a manner
indistinguishable from wild type (WT), although sSLF failed to
stimulate or promote the survival of cells expressing the double
mutant. In contrast, although cells expressing WT or YF719 were
mitogenically stimulated by membrane-bound SLF (mSLF), stimulation of
cells expressing KitYF728 was impaired. Similarly, cells expressing WT
or YF719 receptors were stimulated by plate-bound anti-Kit antibodies,
whereas cells expressing the YF728 receptor were not stimulated.
Neomycin sulfate, a PLC antagonist, inhibited cells expressing YF719
receptors stimulated by sSLF. Neomycin also inhibited cells expressing
the WT receptor that were stimulated by mSLF or immobilized anti-Kit
antibodies but did not inhibit stimulation of cells expressing WT
or YF719 receptors by sSLF. 32D cells expressing KitWT, KitYF719, or
KitYF728 were injected into mice and the presence of cells was
evaluated by colony assays 6 to 7 weeks later. Although both KitWT and
KitYF719 expressing cells could be recovered from the spleen and bone
marrow, recovery of KitYF728 cells from these organs was severely
reduced. These results indicate that Kit tyrosine 728 is of particular
importance for mitogenic stimulation by mSLF or immobilized ligand and
is required for full maintenance of cells in vivo, likely through activation of PLC-.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Mithraprabhu and K. L Loveland
Control of KIT signalling in male germ cells: what can we learn from other systems?
Reproduction,
November 1, 2009;
138(5):
743 - 757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hong, V. Munugalavadla, and R. Kapur
c-Kit-Mediated Overlapping and Unique Functional and Biochemical Outcomes via Diverse Signaling Pathways
Mol. Cell. Biol.,
February 1, 2004;
24(3):
1401 - 1410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.-Q. Yao, J.-J. Wu, B.-H. Sun, N. Troiano, M. A. Mitnick, and K. Insogna
The Cell Surface Form of Colony-Stimulating Factor-1 Is Biologically Active in Bone in Vivo
Endocrinology,
August 1, 2003;
144(8):
3677 - 3682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Tan, L. Hong, V. Munugalavadla, and R. Kapur
Functional and Biochemical Consequences of Abrogating the Activation of Multiple Diverse Early Signaling Pathways in Kit. ROLE FOR Src KINASE PATHWAY IN KIT-INDUCED COOPERATION WITH ERYTHROPOIETIN RECEPTOR
J. Biol. Chem.,
March 21, 2003;
278(13):
11686 - 11695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kapur, S. Chandra, R. Cooper, J. McCarthy, and D. A. Williams
Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor
Blood,
July 30, 2002;
100(4):
1287 - 1293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Maddens, A. Charruyer, I. Plo, P. Dubreuil, S. Berger, B. Salles, G. Laurent, and J.-P. Jaffrezou
Kit signaling inhibits the sphingomyelin-ceramide pathway through PLCgamma 1: implication in stem cell factor radioprotective effect
Blood,
July 30, 2002;
100(4):
1294 - 1301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Soboloff and S. A. Berger
Sustained ER Ca2+ Depletion Suppresses Protein Synthesis and Induces Activation-enhanced Cell Death in Mast Cells
J. Biol. Chem.,
April 12, 2002;
277(16):
13812 - 13820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
