ArticleMolecular and cellular biology2012
A switch of G protein-coupled receptor binding preference from phosphoinositide 3-kinase (PI3K)-p85 to filamin A negatively controls the PI3K pathway.
Article in Molecular and cellular biology, 2012. 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, 39 citations in OpenAlex.
- Review
- Sustained generation of neurons destined for neocortex with oxidative metabolic upregulation upon filamin abrogation.iScience · 2024Article
- Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane.Nature communications · 2023Article
- Role of filamin A in the pathogenesis of neuroendocrine tumors and adrenal cancer.Endocrine oncology (Bristol, England) · 2022Review
- Cytoskeletal Remodeling in Cancer.Biology · 2020Review
- Article
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- Anti-metastatic potential of somatostatin analog SOM230: Indirect pharmacological targeting of pancreatic cancer-associated fibroblasts.Oncotarget · 2016Article
- CC chemokine receptor 10 cell surface presentation in melanocytes is regulated by the novel interaction partner S100A10.Scientific reports · 2016Article
- Filamin A Expression Negatively Regulates Sphingosine-1-Phosphate-Induced NF-κB Activation in Melanoma Cells by Inhibition of Akt Signaling.Molecular and cellular biology · 2016Article
- G protein-coupled receptors directly bind filamin A with high affinity and promote filamin phosphorylation.Biochemistry · 2015Article
- Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance.EMBO molecular medicine · 2015Article
- Dopamine and Somatostatin Analogues Resistance of Pituitary Tumors: Focus on Cytoskeleton Involvement.Frontiers in endocrinology · 2015Review
- Complex roles of filamin-A mediated cytoskeleton network in cancer progression.Cell & bioscience · 2013Article
- Dysregulation of RNA polymerase I transcription during disease.Biochimica et biophysica actaReview
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Frequent oncogenic alterations occur in the phosphoinositide 3-kinase (PI3K) pathway, urging identification of novel negative controls. We previously reported an original mechanism for restraining PI3K activity, controlled by the somatostatin G protein-coupled receptor (GPCR) sst2 and involving a ligand-regulated interaction between sst2 with the PI3K regulatory p85 subunit. We here identify the scaffolding protein filamin A (FLNA) as a critical player regulating the dynamic of this complex. A preexisting sst2-p85 complex, which was shown to account for a significant basal PI3K activity in the absence of ligand, is disrupted upon sst2 activation. FLNA was here identified as a competitor of p85 for direct binding to two juxtaposed sites on sst2. Switching of GPCR binding preference from p85 toward FLNA is determined by changes in the tyrosine phosphorylation of p85- and FLNA-binding sites on sst2 upon activation. It results in the disruption of the sst2-p85 complex and the subsequent inhibition of PI3K. Knocking down FLNA expression, or abrogating FLNA recruitment to sst2, reversed the inhibition of PI3K and of tumor growth induced by sst2. Importantly, we report that this FLNA inhibitory control on PI3K can be generalized to another GPCR, the mu opioid receptor, thereby providing an unprecedented mechanism underlying GPCR-negative control on PI3K.
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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.