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)

Okadaic acid, a potent tumor promoter and inhibitor of phosphoserine/threonine protein phosphatases 1 and 2A, produces a large increase in epidermal growth factor (EGF) receptor phosphorylation in several cell types. The increases are limited to phosphoserine and phosphothreonine residues. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a distinct tumor promoter and protein kinase C activator, also induces serine/threonine phosphorylation of the EGF receptor and is known to modulate receptor functions. Comparison of okadaic acid and TPA influences on the EGF receptor show significant differences. Okadaic acid did not promote phosphorylation of Thr-654, a major site of TPA-induced phosphorylation. However, other sites of phosphorylation were similar for the two tumor promoters. In vitro experiments with purified protein phosphatase 2A demonstrate the insensitivity of Thr-654 phosphorylation, which regulates EGF receptor function, to dephosphorylation by this okadaic acid-sensitive protein phosphatase. In contrast to TPA, okadaic acid did not attenuate the tyrosine kinase activity or ligand binding capacity of the EGF receptor. However, okadaic acid did produce a decrease in EGF-stimulated inositol phosphate formation in a manner distinct from that of TPA.
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PMID:Okadaic acid-induced hyperphosphorylation of the epidermal growth factor receptor. Comparison with receptor phosphorylation and functions affected by another tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. 165 56

Multidrug-resistant cells can manifest an increase in epidermal growth factor (EGF) receptor number along with increased P-glycoprotein (Pgp) synthesis. An interrelationship of the two membrane proteins in actinomycin D-resistant Chinese hamster lung cells (DC-3F/AD X) in terms of the effect of EGF on Pgp phosphorylation was investigated. EGF was not a mitogen for the resistant cells, nor was it mitogenic for DC-3F, the parental drug-sensitive line. Brief treatment of DC-3F/AD X cells with EGF resulted in a 30-50% decrease in the level of Pgp phosphorylation, and treatment of the cells with okadaic acid, a specific inhibitor of protein phosphatases-1 and -2A (PP1 and 2A), increased Pgp phosphorylation. Okadaic acid also increased phosphorylation of Pgp in plasma membranes isolated from DC-3F/AD X cells by 30-40%. Protein phosphatase activity in extracts of cells grown in EGF-containing medium was greater by 30% than that of cells grown in standard medium, and okadaic acid inhibited the increases. The results suggested that EGF activated PP1 and PP2A in DC-3F/AD X cells and that Pgp was a substrate for the phosphatases. The properties of Pgp may be modulated by the signalling system transduced by ligand-activated EGF receptor.
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PMID:Crosstalk between epidermal growth factor receptor and P-glycoprotein in actinomycin D-resistant Chinese hamster lung cells. 790 16