Regulation by protein-tyrosine phosphatase PTP2 is distinct from that by PTP1 during Dictyostelium growth and development.

Abstract

We have cloned a gene encoding a second Dictyostelium discoideum protein-tyrosine phosphatase (PTP2) whose catalytic domain has -30 to 39% amino acid identity with those of other PTPs and a 41% amino acid identity with D. discoideum PTP1. Like PTP1, PTP2 is a nonreceptor PTP with the catalytic domain located at the C terminus of the protein. PTP2 Protein-tyrosine kinases (PTKs) initiate and propagate signals in the regulation of growth, morphogenesis, and differentiation. Progression through the cell cycle and the induction of cell proliferation in response to growth factors are regulated by PTKs. Receptor PTKs in Drosophila melanogaster, Caenorhabditis elegans, and mice transduce extracellular morphogenic signals that direct cell fate. The need to regulate these signals is demonstrated by the ability of oncogenic forms of tyrosine kinases to elevate the levels of tyrosine-phosphorylated (pTyr) proteins in cells, leading to the unrestrained growth of neoplasia. Protein-tyrosine phosphatases (PTPs) which selectively dephosphorylate pTyr proteins have been isolated (3, 33). These have been grouped into two structural categories, those that are cytoplasmic or membrane associated and contain a single highly conserved phosphatase domain of -270 amino acids (nonreceptor) and those that span the plasma membrane and contain, in most cases, two copies of this conserved domain (receptor-like). Other more distantly related members of the family act with dual specificity upon phosphoserine and phosphothreonine as well as pTyr substrates. Little is known about the specific biological roles of these proteins, although one of the important insights is that two of the most studied PTPs, CD45, required for T-cell activation (32), and Cdc25,

Identification and functional analysis of a developmentally regulated extracellular signal-regulated kinase gene in Dictyostelium discoideum.

“…We note that PTP1 has a spatial pattern of expression similar to that of PTP2 and ERK1 during the multicellular stages, although it is not known whether these genes are all expressed in overlapping cell populations (42,43 …”

“…Since ERK function is regulated by phosphorylation and dephosphorylation on a threonine and a tyrosine residue, we examined the possible genetic interactions between phosphotyrosine phosphatases and ERK1 function. The functions of two Dictyostelium developmentally regulated phosphotyrosine phosphatases, PTP1 and PTP2, have been previously examined (42,43). ptpl -null cells undergo normal morphogenesis but differentiate more rapidly than the parental strain, while the development of ptp2-null cells is indistinguishable from that of wild-type cells (42,43).…”

“…The functions of two Dictyostelium developmentally regulated phosphotyrosine phosphatases, PTP1 and PTP2, have been previously examined (42,43). ptpl -null cells undergo normal morphogenesis but differentiate more rapidly than the parental strain, while the development of ptp2-null cells is indistinguishable from that of wild-type cells (42,43). ERK1 and His6ERK1 were overexpressed in ptpland ptp2-null cells from the ActlS promoter.…”

Caracterização molecular da proteína DdI-2 e mapeamento de seus domínios de interação com a proteína fosfatase do tipo-1 de Dictyostelium discoideum

“…Ao menos oito tirosinas quinases e três tirosinas fosfatases já foram identificadas, sendo que as primeiras são distintas das tirosina quinases de mamíferos (Tan & Spudich, 1990;Howard et al, 1992;Ramalingam et al, 1993;Howard et al, 1994;Adler et al, 1996;Gamper et al, 1996;Kim et al, 1999). E ainda, por volta de 15 histidina quinases estão presentes em D. discoideum, quatro delas, DhkA, DhkB, DhkC e DokA têm sido estudadas com mais detalhes e estão implicadas no desenvolvimento.…”

Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum

“…In Dictyostelium, several tyrosine phosphatases (PTP1, PTP2, and PTP3) have been characterized (Early et al 2001;Gamper et al 1996;Gamper et al 1999, Howard et al 1992Howard et al 1994). These phosphatases are involved in cell differentiation or stress response signaling, but it is not known if ERK2 is regulated by any of these tyrosine phosphatases.…”