Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many oncogenes encode proteins with a tyrosine kinase activity that appears to be directly involved in the process of transformation. Because these kinases are themselves activated for transformation by tyrosine phosphorylation, proteins which remove phosphate from tyrosine residues, protein tyrosine phosphatases (also termed phosphotyrosine phosphatases and protein phosphotyrosyl phosphatases), are intuitive candidate transformation suppressors. The human PTP1B gene, previously cloned in our laboratory and encoding the low molecular weight protein tyrosine phosphatase PTPase 1B, was introduced into NIH 3T3 cells. Subsequent transformation of these PTPase 1B-expressing cells by an oncogenic form of the human neu gene was suppressed relative to control NIH 3T3 cells. This suppression of transformation was observed in assays for focus formation, anchorage-independent growth, and tumorigenicity. Tumorigenicity assays indicated a complex effect of PTPase 1B expression on transformation.
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PMID:Effect of protein tyrosine phosphatase 1B expression on transformation by the human neu oncogene. 134 14

The HER2/neu gene encodes a receptor tyrosine kinase that is highly homologous to the epidermal growth factor receptor. Overexpression of the receptor in mammary and ovarian carcinoma correlates with poor patient prognosis. To determine how the overexpression of a normal receptor leads to the generation of an oncogenic signal, we compared the patterns of tyrosine phosphorylation in tumor-derived human cell lines expressing high levels of p185HER2/neu. In intact SKBR3 cells, basal phosphorylation of p185HER2/neu was not detected. However, pretreatment of cells with the tyrosine phosphatase inhibitor, sodium orthovanadate, led to the detection of phosphotyrosine on phospholipase C-gamma (PLC-gamma), GTPase-activating protein but not on the RAF-1 kinase. Strikingly, PLC-gamma was detected in a complex which contained multiple tyrosine-phosphorylated polypeptides. This complex was detected only in cytoplasmic fractions and had a distinct composition in different p185HER2/neu-overexpressing cell lines. Although GTPase-activating protein has been found previously in association with proteins of 190 and 62 kDa in fibroblasts, in SKBR3 cells it was found associated with multiple additional tyrosine-phosphorylated polypeptides. These experiments show that SKBR3 cells possess high levels of protein tyrosine phosphatase that can act upon p185HER2/neu. Moreover, they reveal, for the first time, the presence of PLC-gamma and GTPase-activating protein in cytosolic complexes containing a variety of other tyrosine-phosphorylated polypeptides. These observations suggest novel possibilities for the specific definition of receptor-generated signals in tumor cells.
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PMID:Tyrosine phosphatase inhibition permits analysis of signal transduction complexes in p185HER2/neu-overexpressing human tumor cells. 134 42

Motor neurons modulate acetylcholine receptor (AChR) gene expression in skeletal muscle by two signalling pathways: the transmitter-evoked depolarization of muscle membrane inhibits AChR gene transcription throughout the myofibre presumably via activation of a serine/threonine kinase, while the transcription rates of AChR genes in the synaptic region are increased by nerve-derived trophic factors including AChR-inducing activity (ARIA). To gain further insight into these interactions we characterized the receptor for heregulin (HRG)/ARIA in muscle. We showed that HRG increases AChR alpha-subunit mRNA levels via tyrosine phosphorylation of ErbB3 and ErbB2/neu in myotubes. The protein tyrosine phosphatase inhibitor, pervanadate, potentiated the responses to HRG that were in turn blocked by the tyrosine kinase inhibitor erstatin, indicating the relevance of tyrosine phosphorylation to these events. The effects of HRG were inhibited by enhanced cellular serine/threonine phosphorylation which has been implicated in the repression of AChR genes by electrical activity. Immunocytochemical analysis of adult rat muscle revealed that while ErbB2/neu is present throughout the entire surface of the myofibre membrane, ErbB3 expression is exclusively restricted to the endplate suggesting its involvement in synapse-specific transcription of AChR genes by HRG/ARIA.
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PMID:ErbB3 and ErbB2/neu mediate the effect of heregulin on acetylcholine receptor gene expression in muscle: differential expression at the endplate. 755 67

The protein tyrosine phosphatase Epsilon (PTPepsilon) gene gives rise to two physiologically-distinct protein products - a transmembranal, receptor-like form and a cytoplasmic, non-receptor form. Previous studies have suggested a link between expression of transmembranal PTPepsilon and transformation of mouse mammary epithelium specifically by ras or neu, although little is known about the underlying molecular mechanisms; cytoplasmic PTPepsilon is believed to function mainly in hematopoietic tissues. As part of our efforts to understand PTPepsilon function at the molecular level, we demonstrate here that both forms of PTPepsilon associate with the adaptor molecule Grb2 in vivo. Binding is mediated by the SH2 domain of Grb2; this domain binds exclusively to the carboxy-terminal phosphotyrosine of cytoplasmic PTPepsilon(Y638), and probably to additional phosphotyrosine residues in transmembranal PTPepsilon. Through its SH2 domain, Grb2 can constitutively associate with transmembranal PTPepsilon in mammary tumors initiated by ras or neu, and can be induced to associate with cytoplasmic PTPepsilon in Jurkat T-cells following stimulation of T-cell receptor signaling by pervanadate. These findings indicate that tyrosine phosphorylation of PTPepsilon and subsequent binding to Grb may link this phosphatase to downstream events which transduce signals from the cell membrane to its interior.
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PMID:The transmembranal and cytoplasmic forms of protein tyrosine phosphatase epsilon physically associate with the adaptor molecule Grb2. 1049 Aug 39

Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors and Her2/neu breast carcinomas are more aggressive than conventional neoplasms. We studied 64 cases with immunohistochemistry, using 23 antibodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81% of tumors and vimentin was identified in 55%. The mean Ki67 index was 46% (range, 10-90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-kappaB factor, was present in 13% of neoplasms. Epithelial growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR) or c-kit (CD117) was identified in 77% of tumors. Loss of protein tyrosine phosphatase was found in 14%, whereas Akt activation was present in 28%. Several differences were identified between two subtypes of basal breast carcinomas: the pure variant (negative S-100 and actin) was more frequently associated with 'in situ carcinoma' (P=0.019) and pBad overexpression (P=0.098), whereas the myoepithelial variant (positive S-100 or actin) showed more frequent tumor necrosis (P=0.048), vimentin expression (P=0.0001), CD117 expression (P=0.001) and activated caspase-3 (P=0.089). IGF-IR could be as important as EGFR for the growth of these neoplasms. Basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.
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PMID:Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas). 1865 95