A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases

Abstract

The phosphorylation of proteins at tyrosine residues is critical in cellular signal transduction, neoplastic transformation and control of the mitotic cycle. These mechanisms are regulated by the activities of both protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPases). As in the PTKs, there are two classes of PTPases: membrane associated, receptor-like enzymes and soluble proteins. Here we report the isolation of a complementary DNA clone encoding a new form of soluble PTPase, PTP1C. The enzyme possesses a large noncatalytic region at the N terminus which unexpectedly contains two adjacent copies of the Src homology region 2 (the SH2 domain) found in various nonreceptor PTKs and other cytoplasmic signalling proteins. As with other SH2 sequences, the SH2 domains of PTP1C formed high-affinity complexes with the activated epidermal growth factor receptor and other phosphotyrosine-containing proteins. These results suggest that the SH2 regions in PTP1C may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. PTPase activity may thus directly link growth factor receptors and other signalling proteins through protein-tyrosine phosphorylation.

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530

“…This preparative material was digested with CNBr and the digestion products were separated on a 22% SDS ± PAGE gel. The intensity of the phosphorylated Tyr 530 band from Src protein isolated from BT-483 cells was slightly reduced relative to HFF cells (77%) (Figure 4c and d Preliminary analysis of some known tyrosine phosphatases in breast tumor cell lines Several previous reports have suggested possible roles for speci®c PTPases in the development of breast and other cancers (den Hertog et al, 1993;Elson and Leder, 1995;Galaktionov et al, 1995;Pallen, 1993;Shen et al, 1991;Tomic et al, 1995;Zhai et al, 1993), including SH-PTP1, PTP1B, SH-PTP2, PTPalpha, LAR and Cdc25B. We examined the expression of these phosphatases in the four breast tumor cell lines studied here, which we had shown to have higher levels of Src-speci®c phosphatase activity.…”

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).…”