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)

The generation and characterization of Swiss/3T3 cells which stably over-express protein kinase C (PKC)-alpha were previously described by us. In these cells over-expression of PKC-alpha reduced the expression of epidermal growth factor (EGF) receptor molecules [(1990) J. Biol. Chem. 265, 13290-13296]. Here we show that the expression of PDGF-alpha receptors, but not PDGF-beta receptors, was specifically decreased in these cells. Not only were the levels of PDGF-alpha receptor mRNA transcript and protein significantly diminished in the PKC-alpha over-producing cells, but their ability to respond to short- and long-term growth factor signals was appropriately compromised. This was reflected in a reduced tyrosine autophosphorylation signal in response to PDGF-AA, as well as in decreased growth rates of PKC-alpha over-expressing cells when supplied with external PDGF-AA. A similar decrease in PDGF-alpha receptors was also demonstrated in parental Swiss/3T3 cells treated with phorbol esters. Our studies imply that PKC-alpha is involved in a cellular mechanism suppressing the expression of PDGF-alpha receptors in Swiss/3T3 cells. Hence, activation of PKC-alpha or alterations in its cellular levels may affect, in turn, the expression of a specific set of cell surface receptors and their responses to external growth factors.
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PMID:The expression of PDGF-alpha but not PDGF-beta receptors is suppressed in Swiss/3T3 fibroblasts over-expressing protein kinase C-alpha. 814 71

The regulation of adrenal function, including aldosterone production from adrenal glomerulosa cells, is dependent on a variety of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). In many cell types, GPCR-mediated MAPK activation is mediated through transactivation of RTKs, in particular the epidermal growth factor (EGF) receptor (EGF-R). However, the extent to which this cross-communication between GPCRs and RTKs is operative in the adrenal glomerulosa has not been defined. Bovine adrenal glomerulosa cells express receptors for lysophosphatidic acid (LPA) and EGF. In cultured bovine adrenal glomerulosa cells, LPA, which is predominantly coupled to Gi and partially to Gq/protein kinase C alpha and epsilon, caused phosphorylation of Src (at Tyr416), proline-rich tyrosine kinase (Pyk2 at Tyr402), EGF-R, protein kinase B/Akt, extracellularly regulated signal kinases 1/2, and their dependent protein, p90 ribosomal S6 kinase. Overexpression of dominant negative mutants of Ras or EGF-R, and selective inhibition of EGF-R kinase with AG1478, significantly reduced LPA-induced ERK1/2 phosphorylation. However, this was not impaired by inhibition of matrix metalloproteinase (MMP) and heparin-binding EGF. LPA-induced ERK1/2 activation occurs predominantly through EGF-R transactivation by Gi/Src and partly through activation of protein kinase C, which acts downstream of EGF-R and Ras. In contrast, LPA-induced phosphorylation of Shc and ERK1/2 in clonal hepatocytes (C9 cells) was primarily mediated through MMP-dependent transactivation of the EGF-R. These observations in adrenal glomerulosa and hepatic cells demonstrate that LPA phosphorylates ERK1/2 through EGF-R transactivation in a MMP-dependent or -independent manner in individual target cells. This reflects the ability of GPCRs expressed in cell lines and neoplastic cells to utilize distinct signaling pathways that can elicit altered responses compared with those of native tissues.
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PMID:Mechanisms of extracellularly regulated kinases 1/2 activation in adrenal glomerulosa cells by lysophosphatidic acid and epidermal growth factor. 1592 12