MOUSE AND HUMAN SHPS-1 - MOLECULAR-CLONING OF CDNAS AND CHROMOSOMAL LOCALIZATION OF GENES

SHPS-1 (SHP substrate-1) is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SRC homolog y 2 (SH2) domain binding sites, in its cytoplasmic region, Various mit ogens and cell adhesion induce tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, an SH2 domain-containing protei n tyrosine phosphatase, suggesting that SHPS-1 plays a role in cell si gnaling in response to both growth factors and cell adhesion. The mous e and human cDNAs encoding SHPS-1 have now been isolated. The deduced amino acid sequences of rat, human, and mouse SHPS-1 show identities o f 65 to 81 %. In addition to the SH2 domain binding sites, a proline-r ich putative SH3 domain binding site was detected in the cytoplasmic r egion of SHPS-1. Northern blot analysis revealed that human SHPS-1 mRN A is most abundant in brain and that the mouse mRNA is present in embr yos as early as day 7. Fluorescence in situ hybridization localized th e SHPS-1 gene to human chromosome 20p13 and the F3 band of mouse chrom osome 2, Furthermore, interspecific backcross analysis placed the mous e SHPS-1 locus 5.0 centimorgans distal and 1.4 centimorgans proximal t o the microsatellite markers D2Mit63 and D2Mit19, respectively, in a r egion associated with the mutations coloboma (Cm), lethal milk (lm), a nd well-haarig (we). (C) 1997 Academic Press.