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)

In the present study, Western-blot and radioreceptor analyses have revealed the presence of the epidermal growth factor (EGF) receptor in pancreatic acinar membranes. Isolated pancreatic acinar membranes, which allow access of functional antibodies to individual components of the signal transduction cascade, were used to examine EGF-induced regulation of adenylate cyclase activity. Forskolin, vasoactive intestinal peptide (VIP) and to a smaller extent EGF increased cAMP production in pancreatic acinar membranes. Preincubation of the membranes with anti-GS alpha antibody abolished EGF- and VIP-induced cAMP production, but had no effect on forskolin-induced cAMP accumulation. In the presence of either VIP or forskolin, EGF inhibited the VIP- and forskolin-induced cAMP production with an IC50 of 5 nM. Anti-G alpha i1-2 protein antibody, but not anti-G alpha i3 antibody, increased basal cAMP production, indicating that Gi proteins exert an inhibitory influence on basal adenylate cyclase activity. Anti-G alpha i1-2 antibody, but not anti-G alpha i3 antibody, abolished the inhibitory effect of EGF on the forskolin- and VIP-induced cAMP accumulation. A peptide corresponding to the juxtamembrane region in the cytosolic domain of the rat EGF receptor increased cAMP production in pancreatic acinar membranes in an anti-G alpha s antibody-sensitive fashion, whereas the EGF receptor peptide did not mimic the inhibitory effect of the native EGF receptor. The tyrosine kinase inhibitors genistein and pp60v-src (137-157) inhibited both the stimulatory and the inhibitory effects of EGF on cAMP production. Thus the data of the present study show that EGF regulates adenylate cyclase via activation of Gs and Gi proteins by a tyrosine phosphorylation-dependent mechanism in pancreatic acinar membranes. This leads to stimulation of basal and inhibition of forskolin- and VIP-induced adenylate cyclase activity respectively.
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PMID:Epidermal growth factor regulates adenylate cyclase activity via Gs and Gi1-2 proteins in pancreatic acinar membranes. 864 37

Nerve growth factor (NGF) treatment causes a profound down-regulation of epidermal growth factor receptors during the differentiation of PC12 cells. This process is characterized by a progressive decrease in epidermal growth factor (EGF) receptor level measured by 125I-EGF binding, tyrosine phosphorylation, and Western blotting. Treatment of the cells with NGF for 5 days produces a 95% reduction in the amount of [35S]methionine-labeled EGF receptors. This down-regulation does not occur in PC12nnr5 cells, which lack the p140(trk) NGF receptor. However, in PC12nnr5 cells stably transfected with p140(trk), the NGF-induced heterologous down-regulation of EGF receptors is reconstituted in part. NGF-induced heterologous down-regulation, but not EGF-induced homologous down-regulation of EGF receptors, is blocked in Ras- and Src-dominant-negative PC12 cells. Treatment with either pituitary adenylate cyclase-activating peptide (PACAP) or staurosporine stimulates neurite outgrowth in PC12 cell variants, but neither induces down-regulation of EGF receptors. NGF treatment of PC12 cells in suspension induces down-regulation of EGF receptors in the absence of neurite outgrowth. These results strongly suggest a p140(trk)-, Ras- and Src-dependent mechanism of NGF-induced down-regulation of EGF receptors and separate this process from NGF-induced neurite outgrowth in PC12 cells.
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PMID:Down-regulation of epidermal growth factor receptors by nerve growth factor in PC12 cells is p140(trk)-, Ras-, and Src-dependent. 911 Sep 95

In synthetic phenotype vascular smooth muscle cells (VSMC), activation of epidermal growth factor (EGF) receptor (EGFR) induces a sustained increase in intermediate conductance K(Ca) (int-K(Ca); K(Ca)3.1) channels that is essential for proliferation. However, a comparable mechanism has not been identified in native contractile phenotype VSMC, which express large conductance K(Ca) (maxi-K(Ca); K(Ca)1.1) channels, not int-K(Ca) channels. Using patch clamp of freshly isolated contractile VSMC from rat basilar artery, we found that EGF (100 ng ml(-1)) caused hyperpolarization (7.9 +/- 3.9 mV) due to activation of iberiotoxin-sensitive, maxi-K(Ca) channels. The EGFR ligands EGF (100 ng ml(-1)), transforming growth factor alpha (0.4 ng ml(-1)) and heparin-binding EGF (100 ng ml(-1)) all caused a 20% increase in maxi-K(Ca) channel current that was blocked by AG-1478 or by knock-down of EGFR expression using cisterna magna infusion of antisense oligodeoxynucleotide (AS-ODN). In controls, EGFR knock-down, and EGFR gain-of-expression (angiotensin II hypertension), the increase in maxi-K(Ca) current correlated with the abundance of EGFR protein expressed. The EGFR-mediated increase in maxi-K(Ca) channel activity was blocked by inhibiting cAMP-dependent protein kinase (cAK) using KT-5720 or Rp-cAMP, or by inhibiting adenylate cyclase type 5 (AC-5) using 2',5'-dideoxyadenosine or knock-down of AC-5 expression by intracisternal AS-ODN. Direct infusion of EGF into cisterna magna caused up-regulation of proliferating cell nuclear antigen (PCNA) in VSMC that was prevented by coinfusion of iberiotoxin or of AG-1478. Our data, which are consistent with the hypothesis that hyperpolarization is critical for a proliferative response, are the first to implicate AC-5 and maxi-K(Ca) channels in gene activation related to EGFR signalling in native contractile VSMC.
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PMID:Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of PCNA in native contractile rat basilar artery smooth muscle. 1629 43