ArticleMolecular and cellular biology2014
Grb2 promotes integrin-induced focal adhesion kinase (FAK) autophosphorylation and directs the phosphorylation of protein tyrosine phosphatase α by the Src-FAK kinase complex.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Article
- Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts.Science signaling · 2023Article
- Phosphatase regenerating liver 3 participates in Integrinβ1/FAK-Src/MAPK signaling pathway and contributes to the regulation of malignant behaviors in hepatocellular carcinoma cells.Journal of gastrointestinal oncology · 2023Article
- ZINC40099027 promotes monolayer circular defect closure by a novel pathway involving cytosolic activation of focal adhesion kinase and downstream paxillin and ERK1/2.Cell and tissue research · 2022Article
- ITGA5 Promotes Tumor Progression through the Activation of the FAK/AKT Signaling Pathway in Human Gastric Cancer.Oxidative medicine and cellular longevity · 2022Article
- The Role of 17β-Estrogen in Escherichia coli Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation.Infection and immunity · 2021Article
- Protein tyrosine phosphatases in cell adhesion.The Biochemical journal · 2021Review
- Nanopore-mediated protein delivery enabling three-color single-molecule tracking in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation.Journal of cellular and molecular medicine · 2020Review
- Article
- Induction of osteoclast-like cell formation by leptin-induced soluble intercellular adhesion molecule secreted from cancer cells.Therapeutic advances in medical oncology · 2019Article
- Review
- Autophagy promotes degradation of internalized collagen and regulates distribution of focal adhesions to suppress cell adhesion.Biology open · 2017Article
- MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells.Scientific reports · 2017Article
- Hyperbaric oxygen protects type II collagen in interleukin-1β-induced mandibular condylar chondrocyte via inhibiting the JNK/c-Jun signaling pathway.Oncotarget · 2017Article
- Increased PTPRA expression leads to poor prognosis through c-Src activation and G1 phase progression in squamous cell lung cancer.International journal of oncology · 2017Article
- c-CBL regulates melanoma proliferation, migration, invasion and the FAK-SRC-GRB2 nexus.Oncotarget · 2016Article
- Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- TGF-β2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages.Scientific reports · 2015Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The integrin-activated Src-focal adhesion kinase (FAK) kinase complex phosphorylates PTPα at Tyr789, initiating PTPα-mediated signaling that promotes cell migration. Recruitment of the BCAR3-Cas complex by PTPα-phospho-Tyr789 at focal adhesions is one mechanism of PTPα signaling. The adaptor protein Grb2 is also recruited by PTPα-phospho-Tyr789, although the role of the PTPα-Grb2 complex in integrin signaling is unknown. We show that silencing Grb2 expression in fibroblasts abolishes PTPα-Tyr789 phosphorylation and that this is due to two unexpected actions of Grb2. First, Grb2 promotes integrin-induced autophosphorylation of FAK-Tyr397. This is impaired in Grb2-depleted cells and prohibits FAK activation and formation of the Src-FAK complex. Grb2-depleted cells contain less paxillin, and paxillin overexpression rescues FAK-Tyr397 phosphorylation, suggesting that the FAK-activating action of Grb2 involves paxillin. A second distinct role for Grb2 in PTPα-Tyr789 phosphorylation involves Grb2-mediated coupling of Src-FAK and PTPα. This requires two phosphosites, FAK-Tyr925 and PTPα-Tyr789, for Grb2-Src homology 2 (SH2) binding. We propose that a Grb2 dimer links FAK and PTPα, and this positions active Src-FAK in proximity with other, perhaps integrin-clustered, molecules of PTPα to enable maximal PTPα-Tyr789 phosphorylation. These findings identify Grb2 as a new FAK activator and reveal its essential role in coordinating PTPα tyrosine phosphorylation to enable downstream integrin signaling and migration.
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