ArticleJournal of cellular physiology2009
14-3-3beta-Rac1-p21 activated kinase signaling regulates Akt1-mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly.
Article in Journal of cellular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types.Physiological reports · 2025Article
- Review
- Clinical Significance of Combined Epithelial-Mesenchymal Transition Markers Expression and Role of Rac1 in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Expression of Marker PAK1 in Sinonasal Polyposis.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2022Article
- Akt-independent effects of triciribine on ACE2 expression in human lung epithelial cells: Potential benefits in restricting SARS-CoV2 infection.Journal of cellular physiology · 2021Article
- Distinct effects of pharmacological inhibition of stromelysin1 on endothelial-to-mesenchymal transition and myofibroblast differentiation.Journal of cellular physiology · 2021Article
- Phospholipid phosphatase related 1 (PLPPR1) increases cell adhesion through modulation of Rac1 activity.Experimental cell research · 2020Article
- Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion.Pharmacology research & perspectives · 2019Article
- Calling in the CaFrontiers in cellular and infection microbiology · 2019Review
- Interaction between Rho GTPases and 14-3-3 Proteins.International journal of molecular sciences · 2017Review
- Akt1 Controls the Timing and Amplitude of Vascular Circadian Gene Expression.Journal of biological rhythms · 2017Article
- Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein.Cellular microbiology · 2016Article
- Article
- Predicting diabetes mellitus genes via protein-protein interaction and protein subcellular localization information.BMC genomics · 2016Article
- Liposome-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitor IPA-3 limits prostate tumor growth in vivo.Nanomedicine : nanotechnology, biology, and medicine · 2016Article
- Stability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium.Nature communications · 2016Article
- Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development.Developmental biology · 2015Article
- The Akt inhibitor, triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis.British journal of pharmacology · 2015Article
- p70 S6-kinase mediates the cooperation between Akt1 and Mek1 pathways in fibroblast-mediated extracellular matrix remodeling.Biochimica et biophysica acta · 2015Article
- P21 activated kinase-1 mediates transforming growth factor β1-induced prostate cancer cell epithelial to mesenchymal transition.Biochimica et biophysica acta · 2015Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Akt1 belongs to the three-gene Akt family and functions as a serine-threonine kinase regulating phosphorylation of an array of substrates and mediating cellular processes such as cell migration, proliferation, survival, and cell cycle. Our previous studies have established the importance of Akt1 in angiogenesis and absence of Akt1 resulted in impaired integrin activation, adhesion, migration, and extracellular matrix assembly by endothelial cells and fibroblasts. In this study, we identify the downstream signaling pathways activated by Akt1 in the regulation of these cellular events. We demonstrate here that Akt1 is necessary for the growth factor stimulated activation of 14-3-3beta-Rac1-p21 activated kinase (Pak) pathway in endothelial cells and fibroblasts. While activation of Akt1 resulted in translocation of Rac1 to membrane ruffles, enhanced Rac1 activity, Pak1 phosphorylation, and lamellipodia formation, resulting in enhanced adhesion and assembly of fibronectin, inhibition of Akt1 resulted in inhibition of these processes due to impaired Rac1-Pak signaling. Formation of lamellipodia, adhesion, and fibronectin assembly by myristoylated Akt1 expression in NIH 3T3 fibroblasts was inhibited by co-expression with either dominant negative Rac1 or dominant negative Pak1. In contrast, impaired lamellipodia formation, adhesion, and fibronectin assembly by dominant negative-Akt1 expression was rescued by co-expression with either constitutively active-Rac1 or -Pak1. Moreover, previously reported defects in adhesion and extracellular matrix assembly by Akt1(-/-) fibroblasts could be rescued by expression with either active-Rac1 or -Pak1, implying the importance of Rac1-Pak signaling in growth factor stimulated cytoskeletal assembly, lamellipodia formation and cell migration in endothelial cells and fibroblasts downstream of Akt1 activation.
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