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)

Streptomyces and other microorganisms produce antibiotics, and enzyme inhibitors as secondary metabolites. Thus, they could be said as a treasury of organic compounds which have various structures and biological functions. Since oncogene theory has been extensively developed, we have screened oncogene function inhibitors from microorganisms as a new group of microbial secondary metabolites. Erbstatin is an inhibitor of epidermal growth factor (EGF) receptor and p60v-src-associated tyrosine kinase. Its inhibitory pattern vs. peptide is competitive. In cell culture it inhibited both EGF receptor autophosphorylation and internalization. Recently, we have isolated lavendustin A, an extremely potent inhibitor of tyrosine kinase, from Streptomyces. Lavendustin A is a novel compound and about 50 times stronger than erbstatin in inhibiting tyrosine kinase. Oxanosine is an inhibitor of ras oncogene product activity. It induces normal phenotypes in temperature-sensitive Kirsten sarcoma virus-infected rat kidney cells, lowering the intracellular levels of guanine nucleotides. Many oncogenes including src, ras, sis, fms and erbB are known to activate cellular phosphatidylinositol (PI) turnover. Therefore we have screened inhibitors of PI turnover and isolated psi-tectorigenine and pendolmycin from Nocardiopsis and inostamycin from Streptomyces. PI kinase is an enzyme involved in PI turnover pathways. We have isolated 2, 3-dihydroxybenzoic acid from Streptomyces as an inhibitor of PI kinase. These oncogene function inhibitors from microorganisms will be useful for the mechanistic study of oncogene product activities.
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PMID:[Inhibitors of oncogene product functions]. 215 83

We have shown that a type I phosphatidylinositol (PI) kinase activity is associated with the epidermal growth factor (EGF) receptor in a mouse fibroblast cell line expressing human EGF receptors (NRHER5) and that this activity increases dramatically upon treatment of cells with physiologically relevant concentrations of EGF. EGF stimulated a time-dependent increase in EGF receptor-associated PI kinase activity measured in EGF receptor immunoprecipitates. Activation was detected 15 min after the addition of EGF, and it peaked between 1 and 2 hr. Activation of PI kinase was detected with EGF concentrations as low as 10 pM and maximal stimulation occurred at approximately 1 nM. Analysis of deacylated PI phosphate products, and inhibition of the PI kinase activity by nonionic detergent, indicated that the PI kinase described here was type I or PI 3' kinase. These results demonstrate the regulation of a type I PI kinase by EGF and suggest a potential role in the EGF receptor signal transduction pathway.
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PMID:Activated type I phosphatidylinositol kinase is associated with the epidermal growth factor (EGF) receptor following EGF stimulation. 216 78

Retroviral onc genes are derived from cellular proto-oncogenes that may function in normal cellular growth control. The epidermal growth factor (EGF) receptor is the proto-oncogene of erbB; both possess intrinsic protein tyrosine kinase activity, a property shared by several retroviral onc genes. The EGF receptor is a transmembrane glycoprotein with an external EGF binding domain and a cytoplasmic region that is homologous with other tyrosine kinases. erbB lacks the EGF binding and carboxyl terminal regions, which are thought to be important in regulation. The EGF receptor is regulated by several mechanisms: stimulation by ligand binding and self-phosphorylation, inhibition by heterologous phosphorylation and downregulation by ligand. EGF binding stimulates several early events, including phosphatidylinositol (PI) turnover in A431 cells. A PI kinase activity copurifies with the EGF receptor and some other tyrosine kinases, but this is a contaminant as it can be separated from the EGF receptor. Although the role of proto-onc genes in human malignancy is incompletely defined, increased numbers of EGF receptors are present in several types of human tumours. Overexpression of EGF receptors, as occurs in human epidermoid carcinoma A431 cells, can augment cell growth because of increased formation of active ligand:receptor complexes. Gene amplification is the mechanism underlying overexpression of EGF receptors in A431 cells and in some glioblastoma multiforme tumours.
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PMID:The EGF receptor: structure, regulation and potential role in malignancy. 282 44