ArticleThe EMBO journal2002
PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 87 citations in OpenAlex.
- A tandem recruitment site in the pseudokinase scaffold PEAK3 is subject to phosphorylation-dependent regulation and cancer-associated mutations.The Journal of biological chemistry · 2026Article
- The insulin signalling network.Nature metabolism · 2025Review
- An analysis of the role of GAB2 in pan-cancer from a multidimensional perspective.Discover oncology · 2024Article
- Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer.Nature communications · 2019Article
- BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines.Oncogene · 2018Article
- Understanding the mechanism of binding between Gab2 and the C terminal SH3 domain from Grb2.Oncotarget · 2017Article
- Deciphering the link between PI3K and PAK: An opportunity to target key pathways in pancreatic cancer?Oncotarget · 2017Review
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- Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes.Scientific reports · 2016Article
- Article
- ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer.Oncotarget · 2014Article
- Boolean ErbB network reconstructions and perturbation simulations reveal individual drug response in different breast cancer cell lines.BMC systems biology · 2014Article
- Grb2-associated binder-1 is required for neuregulin-1-induced peripheral nerve myelination.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Receptor tyrosine kinase (RTK) signalling in the control of neural stem and progenitor cell (NSPC) development.Molecular neurobiology · 2014Review
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- Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells.Cell communication and signaling : CCS · 2013Article
- Gab2 phosphorylation by RSK inhibits Shp2 recruitment and cell motility.Molecular and cellular biology · 2013Article
- Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors.Leukemia · 2013Article
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- PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heregulin (HRG)-induced tyrosine phosphorylation of the Gab2 docking protein was enhanced by pretreatment with wortmannin, indicating negative regulation via a PI3-kinase-dependent pathway. This represents phosphorylation by the serine/threonine kinase protein kinase B (PKB), since PKB constitutively associates with Gab2, phosphorylates Gab2 on a consensus phosphorylation site, Ser159, in vitro and inhibits Gab2 tyrosine phosphorylation. However, expression of Gab2 mutated at this site (S159A Gab2) not only enhanced HRG-induced Gab2 tyrosine phosphorylation and association with Shc and ErbB2, but also markedly increased tyrosine phosphorylation of ErbB2 and other cellular proteins and amplified activation of the ERK and PKB pathways. The impact of this negative regulation was further emphasized by a potent transforming activity for S159A Gab2, but not wild-type Gab2, in fibroblasts. These studies establish Gab2 as a proto-oncogene, and a model in which receptor recruitment of Gab2 is tightly regulated via an intimate association with PKB. Release of this negative constraint enhances growth factor receptor signalling, possibly since Gab2 binding limits dephosphorylation and disassembly of receptor-associated signalling complexes.
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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.