MPTP-DELTA, A PUTATIVE MURINE HOMOLOG OF HPTP-DELTA, IS EXPRESSED IN SPECIALIZED REGIONS OF THE BRAIN AND IN THE B-CELL LINEAGE

Protein tyrosine phosphatases (PTPs), together with protein tyrosine k inases (PTKs), are involved in the regulation of cell activation, grow th, and differentiation. To further elucidate the fine tuning of cell growth and differentiation through tyrosine phosphorylation, we tried to isolate mouse receptor-type PTP (RPTP) cDNA clones by screening mou se brain cDNA libraries with mouse CD45 PTP domain probes under reduce d-stringency conditions. Characterization of isolated cDNA clones for RPTP showed that the cytoplasmic region contains two tandem repeats of PTP domain of about 230 amino acids with intrinsic phosphatase activi ty. The extracellular region was composed of immunoglobulin (Ig)-like domains and fibronectin type III (FN-III)-like domains. The gene was h ighly homologous to human PTPdelta (HPTPdelta) and thus was named MPTP delta (murine counterpart of HPTPdelta). The MPTPdelta gene appeared t o generate at least three species of mRNA, which differ in the composi tion of the extracellular domain: type A, one Ig-like and four FN-IH-l ike domains; type B, one Ig-like and eight FN-III-like domains; and ty pe C, three Ig-like and eight FN-III-like domains. Interestingly, the 5' untranslated region and the leader peptide of types A and B were co mpletely different from those of type C. Northern (RNA) blot analysis demonstrated that brain, kidney, and heart cells express three mRNA sp ecies of about 7 kb. Antibody directed against part of the extracellul ar domain of type A MPTPdelta recognized a 210-kDa protein in brain an d kidney lysates. In situ hybridization of brain samples revealed that MPTPdelta mRNA is present in the hippocampus, thalamic reticular nucl eus, and piriform cortex, where some Src family PTKs have been also de monstrated to exist. Although MPTPdelta mRNA was not detected in lymph oid tissues, all of the pre-B-cell lines tested and one of three B-cel l lines tested expressed MPTPdelta mRNA, whereas antibody-producing B- cell hybridomas and T-cell and macrophage lines did not. Finally, the MPTPdelta locus was tightly linked to the brown (b) locus on mouse chr omosome 4.