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)

We have previously reported that fodrin (beta subunit), tubulin (alpha subunit) and microtubule-associated proteins (MAPs; MAP2 and tau) are good substrates for the purified insulin receptor kinase (Kadowaki, T., Nishida, E., Kasuga, M., Akiyama, T., Takaku, F., Ishikawa, M., Sakai, H., Kathuria, S., and Fujita-Yamaguchi, Y. (1985) Biochem. Biophys. Res. Commun. 127, 493-500 and Kadowaki, T., Fujita-Yamaguchi, Y., Nishida, E., Takaku, F., Akiyama, T., Kathuria, S., Akanuma, Y., and Kasuga, M. (1985) J. Biol. Chem. 260, 4016-4020). In this study, to investigate the substrate specificities of tyrosine kinases, we have examined the actions of the purified epidermal growth factor (EGF) receptor kinase and Rous sarcoma virus src kinase on purified microfilament- and microtubule-related proteins. Among microfilament-related proteins examined, the purified EGF receptor kinase phosphorylated the beta subunit, but not the alpha subunit, of fodrin on tyrosine residues with a Km below the micromolar range. The fodrin phosphorylation by the EGF receptor kinase was markedly inhibited by F-actin. In contrast, the purified src kinase preferentially phosphorylated the alpha subunit of fodrin on tyrosine residues. Fodrin phosphorylation by the src kinase was not inhibited by F-actin. Among microtubule proteins examined, MAP2 was the best substrate for the EGF receptor kinase. By contrast, src kinase favored phosphorylation of tubulin as compared to MAP2. The peptide mapping of MAP2 phosphorylated by the EGF receptor kinase and by the insulin receptor kinase produced very similar patterns of phosphopeptides, while that of MAP2 phosphorylated by the src kinase gave a distinctly different pattern. When the phosphorylation of the tubulin subunits was examined, the EGF receptor kinase preferred beta subunit to alpha subunit, but the src kinase phosphorylated both alpha and beta subunits to a similar extent. These results, together with our previous results, indicate that the substrate specificities of the EGF receptor kinase and the insulin receptor kinase are very similar, but not identical, while that of the src kinase is distinctly different from that of these growth factor receptor kinases.
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PMID:Substrate specificities of tyrosine-specific protein kinases toward cytoskeletal proteins in vitro. 377 52

Leukotrienes (LTs) and lipoxins (LXs) are lipid mediators that play a key role in regulating acute inflammatory responses. Their roles in neural stem cell (NSC) functions are of interest. We showed here that LTB(4) and LXA(4) regulated proliferation and differentiation of murine NSCs that were isolated from embryo brains. Proliferation of NSCs was stimulated by LTB(4) (3 to 100 nM) and blocked by receptor antagonist (IC(50)=2.7 microM). In contrast, LXA(4), and its aspirin-triggered-15-epi-LXA(4) stable analog attenuated growth of NSCs at as little as 1 nM. Both lipoxygenase (LOX) inhibitors and LTB(4) receptor antagonists caused apoptosis and cell death. Gene chip analysis revealed that growth-related gene expressions such as epidermal growth factor (EGF) receptor, cyclin E, p27, and caspase 8 were tightly regulated by LTB(4); LXA(4) gave the opposite gene expressions. In addition to proliferation, LTB(4) induced differentiation of NSCs into neurons as monitored by neurite outgrowth and MAP2 expression. These results indicate for the first time that LTB(4) and LXA(4) directly regulate proliferation and differentiation of NSCs, suggesting these new pathways may be useful in restoring stem cells.
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PMID:Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation. 1694 Jan 50

Overexpression of EGFr and c-erbB-2 is related to poor prognosis in a variety of cancers including gastric cancer. Thus: the ability to modulate the functional activity of these receptors is an attractive target for diagnostic intervention. In this study we examined the effect of a well characterised tyrosine kinase inhibitor (RG13022) on the cellular proliferation and EGF activated tyrosine kinase signalling pathway of two primary gastric cell lines: MKN45 and N87. RG13022 has a dose dependent, antiproliferative effect on both gastric cell lines when grown either in serum-free conditions or in the presence of FCS. Western blotting revealed RG13022 caused an inhibition of EGF stimulated tyrosine phosphorylation of EGFr in A431 cells and both EGFr and c-erbB-2 in MKN45 cells. No clear modulation of EGFr or c-erbB-2 phosphorylation was observed in N87 cells. In both A431 cells and N87 cells (which overexpress EGFr and c-erbB-2 respectively) exposed to EGF, MAP2 kinase immunoblot analysis resulted in the detection of a second protein band with reduced migration in SDS-PAGE. In N87 cells, this protein appeared to co-mi,orate with a strongly tyrosine phosphorylated protein, which suggests that it is a hyper-phosphorylated form of MAP2 kinase. However, treatment with RG13022, whilst inhibiting phosphorylation of this protein, did not prevent a shift in gel mobility (suggestive of activation) of MAP2 kinase in response to EGF. These findings demonstrate that the tyrphostin RG13022 inhibits cell proliferation of two primary gastric cancer cell lines. Investigation of intracellular signalling pathways suggests that alterations in intracellular signalling are responsible for the actions of RG 13022 in these cells. The biochemical analysis revealed that in N87 and A431, cells which overexpress c-erbB-2 and EGFr respectively, the tyrphostin affects the MAP2 kinase immunoreactivity and migration on SDS gels but fails to affect this protein in the MKN45 cell line. This data questions the usefulness of MAP2 kinase gel shift assays as markers of activation but supports the further development of tyrosine kinase inhibitors as potential inhibitors of gastric tumour proliferation.
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PMID:Growth inhibition of gastric cancer cell lines by the tyrphostin RG13022 and its effects on intracellular signalling. 2154 1