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)

Signalling through epidermal growth factor (EGF) receptor leads to several cellular responses including cell division and cell migration. Since EGF receptors are expressed on normal mesothelial cells, this study investigated whether EGF receptor ligands act as chemoattractants on these cells. The study used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV and the nonmatrix adhesive molecule poly-L-lysine, for the migration studies. Normal mesothelial cells migrated to EGF receptor ligands such as EGF, transforming growth factor (TGF)-alpha and heparin-binding epidermal growth factor (HB-EGF) at concentrations ranging 0.024-100 ng x mL(-1) (with a peak stimulation at 6.25 ng x mL(-1)), if matrix proteins were present as adhesive substrates. This migration was integrin-dependent, since the same cells failed to migrate in the absence of extracellular matrix molecules or when the Boyden chamber assay was performed in the presence of anti-beta1 integrin monoclonal antibodies. These findings describe for the first time epidermal growth factor receptor ligands acting as chemoattractants on normal mesothelial cells, and that signalling through epidermal growth factor receptors leading to mesothelial cell migration also requires the activation of integrins.
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PMID:Epidermal growth factor receptor ligands are chemoattractants for normal human mesothelial cells. 1051 21

Our recent studies have shown that proliferation of renal proximal tubular cells (RPTC) in the absence of growth factors requires activation of the epidermal growth factor (EGF) receptor. We sought to identify the endogenous EGF receptor ligand and investigate the mechanism(s) by which RPTC proliferate in different models. RPTC expressed both pro- and cleaved forms of heparin-binding epidermal growth factor (HB-EGF) and several metalloproteinases (MMP-2, -3, -9, and ADAM10, ADAM17) that have been reported to cleave HB-EGF. Treatment of RPTC with CRM 197, an inhibitor of HB-EGF binding to the EGF receptor, or downregulation of HB-EGF with small interfering RNA inhibited RPTC proliferation following plating. Furthermore, GM6001 (pan-MMP inhibitor), tumor-necrosis factor protease inhibitor-1 (TAPI-1; MMP and ADAM17 inhibitor), and GW280264X (ADAM10 and -17 inhibitor), but not GI254023X (ADAM10 inhibitor), attenuated the proliferation after plating. Although EGF receptor activation is required for RPTC proliferation after oxidant injury, CRM197, GM6001, and TAPI-1 did not block this response. In contrast, inhibition of Src with PP1 blocked EGF receptor activation and RPTC proliferation after oxidant injury. In addition, PP1 treatment attenuated HB-EGF-enhanced RPTC proliferation. We suggest that RPTC proliferation after plating is mediated by HB-EGF produced through an autocrine/paracrine mechanism and RPTC proliferation following oxidant injury is mediated by Src without involvement of HB-EGF.
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PMID:Heparin-binding epidermal growth factor and Src family kinases in proliferation of renal epithelial cells. 1817 96