Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13.

Abstract

The growth and many functional responses of hematopoietic cells are regulated through phosphorylation of proteins on tyrosine. However, most hematopoietic growth factor receptors and antigen receptors do not contain intrinsic protein kinase activity but nevertheless rapidly induce protein tyrosine phosphorylation (22-24, 31, 40, 42, 48). A variety of observations indicate that these phosphorylations are essential for a mitogenic response. In particular, introduction of protein tyrosine kinases has been shown to abrogate the requirements of hematopoietic cells for their growth factors (8,45) and temperature-sensitive mutants of the v-abl kinase confer a temperature-sensitive phenotype for growth factor dependence (7, 27). More recently, it has been shown that there is a direct correlation between the abilities to support growth and initiate protein tyrosine phosphorylation in a series of altered receptors for erythropoietin (41).The mechanisms by which hematopoietic receptors without intrinsic kinase activity alter protein tyrosine phosphorylation could involve coupling of the receptors to a tyrosinespecific kinase and/or protein tyrosine phosphatase. A role for src-related protein tyrosine kinases has been suggested in several studies. In T cells, Ick associates with CD4 and CD8 and is activated by triggering through these surface receptors (59,60,78,80,81) andfyn associates with the T-cell receptor (56). In mast cells and B cells, lyn kinase has been shown to associate with the immunoglobulin E receptor (13) or surface immunoglobulin M (83), respectively. Recent studies have shown that Ick kinase activity is increased following stimulation of T cells with interleukin 2 (IL-2) (21) and that Ick associates with the IL-2 receptor 3 chain (20).Recent studies have also demonstrated a potential role for protein tyrosine phosphatases in T-cell activation and growth. In particular, T cells which lack the membraneassociated protein tyrosine phosphatase CD45 are unable to respond through the T-cell receptor in either proliferation * Corresponding author.(46) or protein tyrosine phosphorylation (30). It has been hypothesized that CD45 is required for activation of srcrelated kinase Ick orfyn by dephosphorylation of a carboxyl, regulatory site of tyrosine phosphorylation (28). A role for protein tyrosine phosphatases in hematopoietic cell growth has also been speculated about on the basis of the observation that inhibitors of protein tyrosine phosphatases can substitute for growth factors and induce mitogenic responses (73).While a variety of hematopoietic cell protein tyrosine kinases have been characterized, less is known about protein tyrosine phosphatases. The known mammalian protein tyrosine phosphatases fall into two broad categories (15). One class is cytoplasmic and includes protein tyrosine phosphatase 1B (PTP1B) (2, 6, 19), a phosphatase that was initially identified in T cells and termed T-cell protein tyrosine phosphatase (TCPTIP) (9), neuronal phosphatase (STEP) (34), and cytoplasmic phosphatases that contain ...

Reduced Tyk2/SHP-1 interaction and lack of SHP-1 mutation in a kindred of familial hemophagocytic lymphohistiocytosis

“…Sequencing analysis of the cDNA fragment revealed that the coding region sequence is identical to the previously reported human SHP-1 cDNA sequence 13 (data not shown), indicating that the SHP-1 protein of the patient did not have point mutations. In support of this, we found that immunoprecipitated SHP-1 from the patient and the parents had comparable PTPase activities in in vitro PTPase assays (data not shown).…”

“…1,9 Since the motheaten disease is associated with loss of functional hematopoietic cell phosphatase (SHP-1) due to mutations in the SHP-1 gene, 9,10 the clinical and histologic similarities between FHLH and the motheaten disease suggest a potential association of FHLH with abnormalities in SHP-1. 9 SHP-1 11 is a cytoplasmic protein tyrosine phosphatase predominantly expressed in cells of the hematopoietic system 12,13 and is also termed PTP1C, 14 SHPTP1, 15 SHP. 16 It has two srchomology 2 (SH2) domains at the amino region and a PTPase domain at the carboxyl terminal region.…”

Deficiency of the Src Homology Region 2 Domain-Containing Phosphatase 1 (SHP-1) Causes Enrichment of CD4+CD25+ Regulatory T Cells

“…Src homology region 2 domain-containing phosphatase 1 (SHP-1) is a non-transmembrane protein tyrosine phosphatase that is expressed predominantly in hemopoietic cells of all lineages and all stages of maturation as well as at lower levels in epithelial cells (21)(22)(23)(24)(25). The existence of a murine genetic model for SHP-1 deficiency has significantly aided our understanding of the biological function of SHP-1 (26,27).…”

The Tyrosine Phosphatase SHP-1 Associates with the sst2 Somatostatin Receptor and Is an Essential Component of sst2-mediated Inhibitory Growth Signaling

“…SHP-1 (also named SHPTP-1, SHP, or HCP) is a non-transmembrane PTPase that contains two Src homology 2 (SH2) domains involved in its association with multiple signaling molecules (17)(18)(19)(20). SHP-1 associates in vivo with activated growth factor tyrosine kinase receptors such as epidermal growth factor receptor (21).…”