Mouse and Human SHPS-1: Molecular Cloning of cDNAs and Chromosomal Localization of Genes

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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 homology 2 (SH2) domain binding sites, in its cytoplasmic region. Various mitogens and cell adhesion induce tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, an SH2 domain-containing protein tyrosine phosphatase, suggesting that SHPS-1 plays a role in cell signaling in response to both growth factors and cell adhesion. The mouse and human cDNAs encoding SHPS-1 have now been isolated. The deduced amino acid sequences of rat , human, and mouse SHPS-1 show identities of 65 to 81 %. In addition to the SH2 domain binding sites, a proline-rich putative SH3 domain binding site was detected in the cytoplasmic region of SHPS-1. Northern blot analysis revealed that human SHPS-1 mRNA is most abundant in brain and that the mouse mRNA is present in embryos as early as day 7. Fluorescence in situ hybridization localized the SHPS-1 gene to human chromosome 20p13 and the F3 band of mouse chromosome 2. Furthermore, interspecific backcross analysis placed the mouse SHPS-1 locus 5.0 centimorgans distal and 1.4 centimorgans proximal to the microsatellite markersD2Mit63andD2Mit19,respectively, in a region associated with the mutations coloboma (Cm), lethal milk (lm), and wellhaarig (we).