|
|
 Previous Article | Table of Contents | Next Article 
Structure-function relationships of stem cell factor: an analysis based on
a series of human-murine stem cell factor chimera and the mapping of a
neutralizing monoclonal antibody
JV Matous, K Langley and K Kaushansky
Division of Hematology, University of Washington Seattle 98195, USA.
Although much is now known about the biological properties of the c-kit
receptor and its ligand, stem cell factor (SCF), little is known of the
structural basis for the binding and function of this hematopoietic
cytokine. By analyzing the activities of chimeric interspecies and
homologue muteins and epitope mapping of a monoclonal antibody (MoAb) to
the human protein, we have found that three distinct regions of SCF are
essential for full biological function. Homologue and interspecies swapping
of polypeptide sequences between the amino terminus and G35, between L79
and N97, and between R121 and D128 reduced or eliminated the ability of the
chimera to act in synergy with murine granulocyte- macrophage
colony-stimulating factor (GM-CSF) to promote hematopoietic colony
formation. Moreover, a nonconformation-dependent MoAb that neutralizes
human, but not murine SCF, was found to bind to residues within the L79-N97
segment of the human homologue. As these three regions localize to the
putative first, third, and fourth helices of the protein, findings
remarkably similar to previous studies of cytokines as diverse as growth
hormone, GM-CSF, and interleukin (IL)-4, our results suggest that cytokines
of multiple classes share a common functional organization.
Volume 88,
Issue 2,
pp. 437-444,
07/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. H. Martin, P. S. Woll, Z. Ni, J. C. Zuniga-Pflucker, and D. S. Kaufman
Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells
Blood,
October 1, 2008;
112(7):
2730 - 2737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, J. Li, C. Ying Wang, A. H. Yan Kwok, and F. C. Leung
Epidermal Growth Factor (EGF) Receptor Ligands in the Chicken Ovary: I. Evidence for Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Potential Oocyte-Derived Signal to Control Granulosa Cell Proliferation and HB-EGF and Kit Ligand Expression
Endocrinology,
July 1, 2007;
148(7):
3426 - 3440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
S. Chandra, R. Kapur, N. Chuzhanova, V. Summey, D. Prentice, J. Barker, D. N. Cooper, and D. A. Williams
A rare complex DNA rearrangement in the murine Steel gene results in exon duplication and a lethal phenotype
Blood,
November 15, 2003;
102(10):
3548 - 3555.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Linden and K. Kaushansky
The Glycan Domain of Thrombopoietin (TPO) Acts in trans to Enhance Secretion of the Hormone and Other Cytokines
J. Biol. Chem.,
September 13, 2002;
277(38):
35240 - 35247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rajaraman, W. S. Davis, A. Mahakali-Zama, H. K. Evans, L. B. Russell, and M. A. Bedell
An Allelic Series of Mutations in the Kit ligand Gene of Mice. I. Identification of Point Mutations in Seven Ethylnitrosourea-Induced KitlSteel Alleles
Genetics,
September 1, 2002;
162(1):
331 - 340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zhang, R. Zhang, A. Joachimiak, J. Schlessinger, and X.-P. Kong
Crystal structure of human stem cell factor: Implication for stem cell factor receptor dimerization and activation
PNAS,
July 5, 2000;
97(14):
7732 - 7737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Lyman and S. E. W. Jacobsen
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
Blood,
February 15, 1998;
91(4):
1101 - 1134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. C. Broudy
Stem Cell Factor and Hematopoiesis
Blood,
August 15, 1997;
90(4):
1345 - 1364.
[Full Text]
[PDF]
|
|
|
|
|
