title: Gab1 amplifies signaling in response to low-intensity stimulation by HGF.
abstract: The receptor tyrosine kinases EGFR and Met induce phosphorylation of the docking protein Gab1, and there is evidence that Gab1 may have a role in the signaling from these receptors. Studying hepatocytes, we previously found that although Gab1 mechanistically interacted in different ways with EGFR and Met, it was involved in mitogenic signaling induced by both EGF and HGF. It has been reported that in EGFR, Gab1 is required particularly at a low dose of EGF. Whether this also applies to HGF/Met signaling has not been investigated. We have studied the role of Gab1 in activation of the Akt and ERK pathways at low- and high-intensity stimulation with EGF and HGF in cultured hepatocytes. In cells where Gab1 was depleted by a specific Gab1-directed siRNA, the EGF-induced phosphorylation of ERK was lowered and HGF-induced phosphorylation of both ERK and Akt was substantially reduced. These effects were more marked at low-dose HGF stimulation. The inhibitory consequence of Gab1 depletion was particularly pronounced for HGF-induced Akt phosphorylation. The results suggest that Gab1 is an important signal amplifier for low-intensity stimulation by HGF.
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aasrum
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.
authors.forename: John
authors.initials: J
authors.lastname: Ødegård
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.|Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316, Oslo, Norway.
authors.forename: Gunn Hege
authors.initials: GH
authors.lastname: Thoresen
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.|Department of Oral Biology, University of Oslo, P.O. Box 1052, Blindern, 0316, Oslo, Norway.|Department of Paediatric Dentistry and Behavioural Science, Faculty of Dentistry, University of Oslo, P.O. Box 1052, Blindern, 0316, Oslo, Norway.
authors.forename: Ingvild J
authors.initials: IJ
authors.lastname: Brusevold
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.
authors.forename: Dagny L
authors.initials: DL
authors.lastname: Sandnes
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, P.O. Box 1057, Blindern, 0316, Oslo, Norway.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Christoffersen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: C490896:Gab1 protein, rat; D010750:Phosphoproteins; D017228:Hepatocyte Growth Factor
keywords: EGF; ERK; Gab1; HGF; PI3K; hepatocytes