ArticleMolecular biology of the cell2014
PKCβII acts downstream of chemoattractant receptors and mTORC2 to regulate cAMP production and myosin II activity in neutrophils.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Long-range mutual activation establishes Rho and Rac polarity during cell migration.Nature cell biology · 2026Article
- Quantitative Monitoring of GPCR-Mediated Spatiotemporal IPMethods in molecular biology (Clifton, N.J.) · 2024Article
- Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration.Molecular biology of the cell · 2023Article
- Review
- Functional implications of neutrophil metabolism during ischemic tissue repair.Current opinion in pharmacology · 2022Review
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- Nanometric targeting of type 9 adenylyl cyclase in heart.Biochemical Society transactions · 2019Review
- Insights into the Regulatory Properties of Human Adenylyl Cyclase Type 9.Molecular pharmacology · 2019Article
- Biomarkers from circulating neutrophil transcriptomes have potential to detect unruptured intracranial aneurysms.Journal of translational medicine · 2018Article
- The role of mTOR-mediated signals during haemopoiesis and lineage commitment.Biochemical Society transactions · 2018Review
- Function of Adenylyl Cyclase in Heart: the AKAP Connection.Journal of cardiovascular development and disease · 2018Review
- Two independent but synchronized Gβγ subunit-controlled pathways are essential for trailing-edge retraction during macrophage migration.The Journal of biological chemistry · 2017Article
- CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.Molecular cancer research : MCR · 2017Article
- Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.Nature reviews. Nephrology · 2016Review
- Dynamic regulation of neutrophil polarity and migration by the heterotrimeric G protein subunits Gαi-GTP and Gβγ.Science signaling · 2016Article
- Non-muscle myosin II in disease: mechanisms and therapeutic opportunities.Disease models & mechanisms · 2015Review
- Regulation of innate immune cell function by mTOR.Nature reviews. Immunology · 2015Review
- mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis.The Journal of cell biology · 2015Article
- Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis.Nature reviews. Nephrology · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chemotaxis is a process by which cells polarize and move up a chemical gradient through the spatiotemporal regulation of actin assembly and actomyosin contractility, which ultimately control front protrusions and back retractions. We previously demonstrated that in neutrophils, mammalian target of rapamycin complex 2 (mTORC2) is required for chemoattractant-mediated activation of adenylyl cyclase 9 (AC9), which converts ATP into cAMP and regulates back contraction through MyoII phosphorylation. Here we study the mechanism by which mTORC2 regulates neutrophil chemotaxis and AC9 activity. We show that inhibition of protein kinase CβII (PKCβII) by CPG53353 or short hairpin RNA knockdown severely inhibits chemoattractant-induced cAMP synthesis and chemotaxis in neutrophils. Remarkably, PKCβII-inhibited cells exhibit specific and severe tail retraction defects. In response to chemoattractant stimulation, phosphorylated PKCβII, but not PKCα, is transiently translocated to the plasma membrane, where it phosphorylates and activates AC9. mTORC2-mediated PKCβII phosphorylation on its turn motif, but not its hydrophobic motif, is required for membrane translocation of PKCβII. Inhibition of mTORC2 activity by Rictor knockdown not only dramatically decreases PKCβII activity, but it also strongly inhibits membrane translocation of PKCβII. Together our findings show that PKCβII is specifically required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis.
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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.