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

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 W₁ 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.