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 response to nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) receptor activated Ras/extracellular signal-regulated kinase (ERK) signaling, PC12 cells undergo a prototypical neuronal differentiation program, characterized by neurite extension and upregulation of voltage-gated ion channels. The epidermal growth factor (EGF) receptor also activates Ras/ERK signaling, but produces proliferation instead of differentiation. In the presence of depolarizing concentrations of KCl, however, EGF elicits neurite outgrowth through the synergistic actions of the Ras/ERK and cAMP signaling pathways. To assess if EGF and KCl/cAMP elicit the same suite of differentiation events as does NGF and bFGF, we used patch clamp recording to determine if EGF in the presence of KCl or a cAMP agonist also induced physiological differentiation as defined by upregulation of ion channels. Chronic NGF treatment of PC12 cell cultures elicited robust morphological differentiation, a threefold increase in mean calcium channel current density, and an eightfold increase in mean sodium channel current density. Sibling cultures chronically treated with EGF in the presence of high KCl or a cAMP agonist also displayed morphological differentiation, but had calcium channel current densities which were no larger than untreated, undifferentiated cells. Additionally, the increase in mean sodium channel current density induced by EGF in the presence of KCl or cAMP was no greater than the increase observed with EGF alone. Thus, although EGF in the presence of KCl or cAMP is sufficient to induce morphological differentiation as defined by neurite outgrowth, synergism of the Ras/ERK and cAMP/PKA signaling pathways is not sufficient to promote the fully physiologically differentiated PC12 phenotype.
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PMID:EGF in combination with depolarization or cAMP produces morphological but not physiological differentiation in PC12 cells. 898 Dec 34

Growth factor receptor tyrosine kinase (RTK)-activated signaling pathways are well established regulators of neuronal growth and development, but whether these signals provide mechanisms for acute modulation of neuronal activity is just beginning to be addressed. We show in pheochromocytoma (PC12) cells that acute application of ligands for both endogenous RTKs [trkA, basic FGF (bFGF) receptor, and epidermal growth factor (EGF) receptor] and ectopically expressed platelet-derived growth factor (PDGF) receptors rapidly inhibits whole-cell sodium channel currents, coincident with a hyperpolarizing shift in the voltage dependence of inactivation. Sodium channel inhibition by trkA and PDGF receptors is mutually occlusive, suggestive of a common signal transduction mechanism. Furthermore, specific inhibitors for trkA and PDGF RTK activities abrogate sodium channel inhibition in response to NGF and PDGF, respectively, showing that the intrinsic RTK activity of these receptors is necessary for sodium channel inhibition. Use of PDGF receptor mutants deficient for specific signaling activities demonstrated that this inhibition is dependent on RTK interaction with Src but not with other RTK-associated signaling molecules. Inhibition was also compromised in cells expressing dominant-negative Ras. These results suggest a possible mechanism for acute physiological actions of RTKs, and they indicate regulatory functions for Ras and Src that may complement the roles of these signaling proteins in long-term neuronal regulation.
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PMID:Growth factor receptor tyrosine kinases acutely regulate neuronal sodium channels through the src signaling pathway. 942 1