Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tyrosine phosphorylation is a key regulator of cell growth regulation and, when aberrant, is linked with the process of oncogenic transformation. Since tyrosine phosphatases (PTP) reverse phosphorylation mediated by tyrosine kinases (PTK), it has been hypothesized, but insufficiently studied to date, that PTPs function as tumor suppressors. Alternatively, PTPs may augment signal transduction by repriming substrates. To begin to assess the role of PTPs in ovarian cancer cell growth regulation, PTP partial cDNAs were cloned from the OVCA 433 ovarian cancer cell line using RT/PCR and degenerate oligonucleotide primers for the PTP consensus domain. Thirteen partial cDNAs were isolated, the sequences of which, when compared to GenBank, suggested that they were derived from PTP family members. These included PTP-alpha, PTP-gamma, LAR, PTP-delta, T-cell PTP, PTP-2A(1D), PTP-1B, PTP-1C, PTP-H1, PTP-PEST, PTP-Gallus, and two isolates which potentially represent novel PTPs. Steady-state expression analyses revealed that PTP-1B expression was undetectable in normal epithelium but was expressed in four of five ovarian cancer cell lines. In contrast, the expression of two SH2-containing PTPs, PTP-1C and PTP-2A, was detected in the normal ovarian epithelium but lost from one or more ovarian cancer cell lines. Finally, PTP-1B, PTP-alpha, and PTP-H1 expression was increased following HER-2/neu transfection of ovarian cancer cell lines. These results suggest that both normal ovarian epithelial cells and ovarian cancer cells express multiple PTPs. Further, some PTPs are differentially expressed between normal ovarian epithelium and ovarian cancer cells. Intriguingly, the transfection and increased expression of the prognostically significant HER-2/neu PTK induced a selective increase in the expression of the PTP-alpha, PTP-1B, and PTP-H1 tyrosine phosphatases.
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PMID:Transfection of human ovarian cancer cells with the HER-2/neu receptor tyrosine kinase induces a selective increase in PTP-H1, PTP-1B, PTP-alpha expression. 862 39

Treatment of HC11 mammary epithelial cells with the lactogenic hormone PRL promotes differentiation and induction of milk protein gene expression via stimulation of the Janus kinase (JAK)/signal transducer and activator of transcription pathway. We have previously shown that autocrine activation of epidermal growth factor (EGF) receptor interferes with normal PRL-induced differentiation. Here we show that PRL activation of JAK2 was dramatically reduced in HC11 cells pretreated with EGF, demonstrating that the target of EGF receptor activation is JAK2 kinase. Using an in-gel protein tyrosine phosphatase (PTP) assay, we observed that the activity of a 125-kDa PTP was up-regulated in HC11 cells in response to EGF. A specific antiserum was used to demonstrate that the 125-kDa PTP was PTP-PEST and to show that EGF treatment of HC11 cells led to an increase in the level of PTP-PEST. In intact HC11 cells, PTP-PEST was constitutively associated with JAK2, and in response to EGF treatment there was an increased level of PTP-PEST in JAK2 complexes. An in vitro phosphatase assay, using PRL-activated JAK2 as the substrate and lysates from HC11 cells as the source of PTP-PEST, revealed that JAK2 could serve as a PTP-PEST substrate. However, in intact cells the regulation of JAK2 by PTP-PEST was complex, since transient overexpression of PTP-PEST had a negligible effect on PRL-induced JAK2 activation. EGF's negative influence on JAK2 activity was blocked by actinomycin D treatment of HC11 cells, suggesting that EGF induced a protein that mediated the effects of PTP-PEST on JAK2. In support of this model, PTP-PEST-containing lysates from EGF-treated HC11 cells dephosphorylated JAK2 to a greater extent than lysates prepared from control cells.
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PMID:The protein tyrosine phosphatase-PEST is implicated in the negative regulation of epidermal growth factor on PRL signaling in mammary epithelial cells. 1173 19