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Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1

Nature Genetics volume 13, pages 309–315 (1996)Cite this article

Abstract

Protein tyrosine phosphorylation plays a key role in regulating eukaryotic cell proliferation and differentiation. Genetic analysis in invertebrates has been invaluable for dissecting the signalling events downstream of receptor tyrosine kinases (RTKs). We have used this approach in mammals to analyse the interactions between the Kit RTK encoded by the murine Dominant white spotting (W) locus and the Shp1 protein tyrosine phosphatase, the product of the murine motheaten (me) gene. Homozygosity for mutations in both W and me ameliorates aspects of both the me and W phenotypes, including the lethal lung disease associated with me and the embryonic lethality and mast cell deficiency associated with W, demonstrating that the Kit receptor plays a role in the pathology of the me phenotype and conversely that Shp1 negatively regulates Kit signalling in vivo.

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Authors and Affiliations

  1. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Room 982, Mount Sinai Hospital, Toronto, Ontario, M5G1X5, Canada

    Robert F. Paulson, Shirly Vesely, Katharine A. Siminovitch & Alan Bernstein

  2. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada

    Katharine A. Siminovitch & Alan Bernstein

  3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Katharine A. Siminovitch

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Paulson, R., Vesely, S., Siminovitch, K. et al. Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1. Nat Genet 13, 309–315 (1996). https://doi.org/10.1038/ng0796-309

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