Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Cambridge Healthtech Institute

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 12 January 1990:
Vol. 247. no. 4939, pp. 209 - 212
DOI: 10.1126/science.1688471
Prev | Table of Contents | Next

Articles

Science, Vol 247, Issue 4939, 209-212
Copyright © 1990 by American Association for the Advancement of Science

articles

The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase

JC Tan, K Nocka, P Ray, P Traktman, and P Besmer

Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021.

The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
c-Kit Expression and Stem Cell Factor-Induced Hematopoietic Cell Proliferation Are Up-Regulated in Aged B6D2F1 Mice.
A. L. Smith, F. M. Ellison, J. P. McCoy Jr., and J. Chen (2005)
J. Gerontol. A Biol. Sci. Med. Sci. 60, 448-456
   Abstract »    Full Text »    PDF »
HGF regulates the development of cortical pyramidal dendrites.
H. Gutierrez, X. Dolcet, M. Tolcos, and A. Davies (2004)
Development 131, 3717-3726
   Abstract »    Full Text »    PDF »
Attenuation of Experimental Proliferative Vitreoretinopathy by Inhibiting the Platelet-Derived Growth Factor Receptor.
Y. Ikuno, F.-L. Leong, and A. Kazlauskas (2000)
Invest. Ophthalmol. Vis. Sci. 41, 3107-3116
   Abstract »    Full Text »
Guanylyl Cyclases and Signaling by Cyclic GMP.
K. A. Lucas, G. M. Pitari, S. Kazerounian, I. Ruiz-Stewart, J. Park, S. Schulz, K. P. Chepenik, and S. A. Waldman (2000)
Pharmacol. Rev. 52, 375-414
   Abstract »    Full Text »    PDF »
Activating Mutation in the Catalytic Domain of c-kit Elicits Hematopoietic Transformation by Receptor Self-Association Not at the Ligand-Induced Dimerization Site.
T. Tsujimura, K. Hashimoto, H. Kitayama, H. Ikeda, H. Sugahara, I. Matsumura, T. Kaisho, N. Terada, Y. Kitamura, and Y. Kanakura (1999)
Blood 93, 1319-1329
   Abstract »    Full Text »    PDF »
Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development.
D. Parichy, J. Rawls, S. Pratt, T. Whitfield, and S. Johnson (1999)
Development 126, 3425-3436
   Abstract »    PDF »
Fab1p Is Essential for PtdIns(3)P 5-Kinase Activity and the Maintenance of Vacuolar Size and Membrane Homeostasis.
J. D. Gary, A. E. Wurmser, C. J. Bonangelino, L. S. Weisman, and S. D. Emr (1998)
J. Cell Biol. 143, 65-79
   Abstract »    Full Text »    PDF »
The Prolactin Receptor Rescues EpoR-/- Erythroid Progenitors and Replaces EpoR in a Synergistic Interaction With c-kit.
M. Socolovsky, A. E.J. Fallon, and H. F. Lodish (1998)
Blood 92, 1491-1496
   Abstract »    Full Text »    PDF »
Phosphorylation of the Kinase Homology Domain Is Essential for Activation of the A-Type Natriuretic Peptide Receptor.
L. R. Potter and T. Hunter (1998)
Mol. Cell. Biol. 18, 2164-2172
   Abstract »    Full Text »
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities.
S. D. Lyman and S. E. W. Jacobsen (1998)
Blood 91, 1101-1134
   Full Text »    PDF »
Analysis of c-kit Receptor Dimerization by Fluorescence Resonance Energy Transfer.
V. C. Broudy, N. L. Lin, H.-J. Buhring, N. Komatsu, and T. J. Kavanagh (1998)
Blood 91, 898-906
   Abstract »    Full Text »    PDF »
Stem Cell Factor and Hematopoiesis.
V. C. Broudy (1997)
Blood 90, 1345-1364
   Full Text »    PDF »
Loss of functional cell surface transforming growth factor beta  (TGF-beta ) type 1 receptor correlates with insensitivity to TGF-beta in chronic lymphocytic leukemia.
J. F. DeCoteau, P. I. Knaus, H. Yankelev, M. D. Reis, R. Lowsky, H. F. Lodish, and M. E. Kadin (1997)
PNAS 94, 5877-5881
   Abstract »    Full Text »    PDF »
Impaired Steel Factor Responsiveness Differentially Affects the Detection and Long-Term Maintenance of Fetal Liver Hematopoietic Stem Cells In Vivo.
C. L. Miller, V. I. Rebel, C. D. Helgason, P. M. Lansdorp, and C. J. Eaves (1997)
Blood 89, 1214-1223
   Abstract »    Full Text »    PDF »
Mutation of Tyrosines 492/493 in the Kinase Domain of ZAP-70 Affects Multiple T-cell Receptor Signaling Pathways.
D. Mege, V. Di Bartolo, V. Germain, L. Tuosto, F. Michel, and O. Acuto (1996)
J. Biol. Chem. 271, 32644-32652
   Abstract »    Full Text »    PDF »
The dominant white spotting oncogene allele Kit(W-42J) exacerbates XY(DOM) sex reversal.
C. Nagamine and C Carlisle (1996)
Development 122, 3597-3605
   Abstract »    PDF »
A cell- and developmental stage-specific promoter drives the expression of a truncated c-kit protein during mouse spermatid elongation.
C Albanesi, R Geremia, M Giorgio, S Dolci, C Sette, and P Rossi (1996)
Development 122, 1291-1302
   Abstract »    PDF »
Identification, Characterization, and Developmental Regulation of a Receptor Guanylyl Cyclase Expressed during Early Stages of Drosophila Development.
L. McNeil, M. Chinkers, and M. Forte (1995)
J. Biol. Chem. 270, 7189-7196
   Abstract »    Full Text »    PDF »
Inhibin Antagonizes Inhibition of Liver Cell Growth by Activin by a Dominant-negative Mechanism.
J. Xu, K. McKeehan, K. Matsuzaki, and W. L. McKeehan (1995)
J. Biol. Chem. 270, 6308-6313
   Abstract »    Full Text »    PDF »
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.
T Hirata, E Morii, M Morimoto, T Kasugai, T Tsujimura, S Hirota, Y Kanakura, S Nomura, and Y Kitamura (1993)
Development 119, 49-56
   Abstract »    PDF »
W-sash affects positive and negative elements controlling c-kit expression: ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis.
R Duttlinger, K Manova, T. Chu, C Gyssler, A. Zelenetz, R. Bachvarova, and P Besmer (1993)
Development 118, 705-717
   Abstract »    PDF »
Ectopic expression of a c-kitW42 minigene in transgenic mice: recapitulation of W phenotypes and evidence for c-kit function in melanoblast progenitors..
P Ray, K M Higgins, J C Tan, T Y Chu, N S Yee, H Nguyen, E Lacy, and P Besmer (1991)
Genes & Dev. 5, 2265-2273
   Abstract »    PDF »
Molecular basis of mouse developmental mutants..
A D Reith and A Bernstein (1991)
Genes & Dev. 5, 1115-1123
   PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)