REGULATION BY PROTEIN-TYROSINE-PHOSPHATASE PTP2 IS DISTINCT FROM THATBY PTP1 DURING DICTYOSTELIUM GROWTH AND DEVELOPMENT

We have cloned a gene encoding a second Dictyostelium discoideum prote in-tyrosine phosphatase (PTP2) whose catalytic domain has approximate to 30 to 39% amino acid identity with those of other PTPs and a 41% am ino acid identity with D. discoideum PTP1. Like PTP1, PTP2 is a nonrec eptor PTP with the catalytic domain located at the C terminus of the p rotein. PTP2 has a predicted molecular weight of 43,000 and possesses an acidic 58-amino-acid insertion 24 amino acids from the N terminus o f the conserved catalytic domain. PTP2 transcripts are expressed at mo derate levels in vegetative cells and are induced severalfold at the o nset of development. Studies with a PTP2-lacZ reporter gene fusion ind icate that PTP2, like PTP1, is preferentially expressed in prestalk an d anterior-like cell types during the multicellular stages of developm ent. PTP2 gene disruptants (ptp2 null cells) are not detectably altere d in growth and show a temporal pattern of development similar to that of wild-type cells.ptp2 null slugs and fruiting bodies, however, are significantly larger than those of wild-type slugs, suggesting a role for PTP2 in regulating multicellular structures. D. discoideum strains overexpressing PTP2 from the PTP2 promoter exhibit growth rate and de velopmental abnormalities, the severity of which corresponds to the le vel of PTP2 overexpression. Strains with high overexpression of the PT P2 gene grow slowly on bacterial lawns and produce small cells in axen ic medium. When development is initiated in these strains, cells are a ble to aggregate but then stop further morphogenesis for 6 to 8 h, aft er which time a variable fraction of these aggregates continue, with n ormal timing, producing diminutive fruiting bodies. These disruption a nd overexpression phenotypes far PTP2 are distinct from the correspond ing mutant PTP1 phenotypes. Immunoprobing PTP2 mutant strains during g rowth and development with antiphosphotyrosine antibodies reveals seve ral changes in the tyrosine phosphorylation of proteins in PTP2 mutant strains compared with that in wild-type cells. These changes are diff erent from those identified in the previously characterized correspond ing PTP1 disruption and overexpression mutant strains. Thus, although PTP2 and PTP1 are nonreceptor PTPs with similar spatial patterns of ex pression, our findings suggest that they possess distinct regulatory f unctions in controlling D. discoideum growth and development.