ArticleOncogene2001
Gab1 phosphorylation: a novel mechanism for negative regulation of HGF receptor signaling.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 48 citations in OpenAlex.
- Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants.GeroScience · 2026Article
- The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies.Frontiers in oncology · 2024Review
- The Role of GAB1 in Cancer.Cancers · 2023Review
- Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis.International journal of cardiology · 2015Review
- Pleiotropic Activities of HGF/c-Met System in Testicular Physiology: Paracrine and Endocrine Implications.Frontiers in endocrinology · 2014Review
- Identification of a new Sprouty protein responsible for the inhibition of the Bombyx mori nucleopolyhedrovirus reproduction.PloS one · 2014Article
- Article
- Protein tyrosine phosphatase-1B regulates the tyrosine phosphorylation of the adapter Grb2-associated binder 1 (Gab1) in the retina.Cell communication and signaling : CCS · 2013Article
- Silencing of c-Met by RNA interference inhibits the survival, proliferation, and invasion of nasopharyngeal carcinoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2011Article
- Cell signaling by receptor tyrosine kinases.Cell · 2010Review
- Function, regulation and pathological roles of the Gab/DOS docking proteins.Cell communication and signaling : CCS · 2009Article
- Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice.PloS one · 2008Article
- ADPKD: molecular characterization and quest for treatment.Clinical and experimental nephrology · 2005Review
- PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2.The EMBO journal · 2002Article
- SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transduction by HGF receptor, the tyrosine kinase encoded by the MET oncogene, switches on a genetic program called 'invasive growth' inducing epithelial cell dissociation, migration, growth, and ultimately leading to differentiation into branched tubular structures. Sustained tyrosine phosphorylation of the downstream adaptor protein Gab1 is required for the HGF response. Here we show that serine/threonine phosphorylation of Gab1 provides a control mechanism for negative regulation. Treatment with okadaic acid, a potent inhibitor of the serine/threonine protein phosphatases PP1 and PP2A, was followed by activation of a number of serine/threonine kinases, hyper-phosphorylation in serine and threonine of Gab1 and severe inhibition of the HGF-induced biological responses. Under these conditions, Gab1 was found to be concomitantly hypo-phosphorylated in tyrosine, and thus endowed with reduced ability to recruit SH2 containing signal transducers such as PI3 kinase. Among the serine-threonine kinases activated by PP1 and PP2A inhibition, we found that PKC-alpha and PKC-beta1 are required for negative regulation of Gab1. These data provide a novel negative mechanism for the HGF receptor signaling pathways and highlight a potentially useful target for inhibitors of invasive growth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.