ArticleThe Journal of biological chemistry2010
A novel cross-talk in diacylglycerol signaling: the Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Distinctive requirement of PKCε in the control of Rho GTPases in epithelial and mesenchymally transformed lung cancer cells.Oncogene · 2019Article
- Review
- The RacGAP β-Chimaerin is essential for cerebellar granule cell migration.Scientific reports · 2018Article
- Rho GTPases as therapeutic targets in cancer (Review).International journal of oncology · 2017Review
- Characterization of a P-Rex1 gene signature in breast cancer cells.Oncotarget · 2016Article
- β3-chimaerin, a novel member of the chimaerin Rac-GAP family.Molecular biology reports · 2014Article
- PKC signaling in glioblastoma.Cancer biology & therapy · 2013Review
- PKCα phosphorylation of RhoGDI2 at Ser31 disrupts interactions with Rac1 and decreases GDI activity.Oncogene · 2013Article
- Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol.Nature communications · 2013Article
- Activation of nuclear factor κB (NF-κB) in prostate cancer is mediated by protein kinase C epsilon (PKCepsilon).The Journal of biological chemistry · 2012Article
- Rac signaling in breast cancer: a tale of GEFs and GAPs.Cellular signalling · 2012Review
- Non-small cell lung carcinoma cell motility, rac activation and metastatic dissemination are mediated by protein kinase C epsilon.PloS one · 2012Article
- Ligand-dependent perturbation of the conformational ensemble for the GPCR β2 adrenergic receptor revealed by HDX.Structure (London, England : 1993) · 2011Article
- Rac-dependent doubling of HeLa cell area and impairment of cell migration and cell cycle by compounds from Iris germanica.Protoplasma · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Although the family of chimaerin Rac-GAPs has recently gained significant attention for their involvement in development, cancer, and neuritogenesis, little is known about their molecular regulation. Chimaerins are activated by the lipid second messenger diacylglycerol via their C1 domain upon activation of tyrosine kinase receptors, thereby restricting the magnitude of Rac signaling in a receptor-regulated manner. Here we identified a novel regulatory mechanism for beta2-chimaerin via phosphorylation. Epidermal growth factor or the phorbol ester phorbol 12-myristate 13-acetate caused rapid phosphorylation of beta2-chimaerin on Ser(169) located in the SH2-C1 domain linker region via protein kinase Cdelta, which retained beta2-chimaerin in the cytosol and prevented its C1 domain-mediated translocation to membranes. Furthermore, despite the fact that Ser(169) phosphorylation did not alter intrinsic Rac-GAP activity in vitro, a non-phosphorylatable beta2-chimaerin mutant was highly sensitive to translocation, and displayed enhanced association with activated Rac, enhanced Rac-GAP activity, and anti-migratory properties when expressed in cells. Our results not only revealed a novel regulatory mechanism that facilitates Rac activation, but also identified a novel mechanism of cross-talk between diacylglycerol receptors that restricts beta2-chimaerin relocalization and activation.
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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.