COMPARISON OF CD45 EXTRACELLULAR DOMAIN SEQUENCES FROM DIVERGENT VERTEBRATE SPECIES SUGGESTS THE CONSERVATION OF 3 FIBRONECTIN TYPE-III DOMAINS

Mammalian CD45 is a transmembrane protein tyrosine phosphatase express ed by all nucleated cells of hematopoietic origin. In lymphocytes, CD4 5 is required for Ag-induced signal transduction due to its ability to positively regulate Src family members, The mechanisms by which CD45 function is regulated are unknown. Indeed, the interactions of CD45 ex tracellular domains are largely undefined. To gain insight into potent ially important regions of the extracellular domain, we sought to iden tify conserved features from divergent species, cDNAs encoding the put ative CD45 homologue from Heterodontus francisci (horned shark) were i solated. The cDNA sequence predicts a protein of 1200 amino acids that contains a 452-amino acid extracellular domain, a 22-amino acid trans membrane region, and a 703-amino acid cytoplasmic domain. Alignment se arches revealed that the Heterodontus cytoplasmic domain sequence was most identical to mammalian CD45 and a transmembrane protein tyrosine phosphatase sequence identified from chickens, ChPTP lambda. A dendrog ram with other transmembrane protein tyrosine phosphatase sequences su ggest that the Heterodontus and chicken sequences represents CD45 orth ologues for their respective species. Analysis of vertebrate CD45 extr acellular domain sequences indicates the conservation of three structu ral regions: a region containing potential O-linked carbohydrate sites , a cysteine-containing region, and a region containing three fibronec tin type III domains. For each vertebrate species, multiple isoforms a re generated by alternative splicing of three exons that encode a port ion of the region containing potential O-linked glycosylation sites. T hese studies provide evidence for a conservation in CD45 extracellular domain structure between divergent species and provide a basis for un derstanding CD45 extracellular domain interactions.