Control of Akt activity and substrate phosphorylation in cells

Yudushkin, Ivan

doi:10.1002/iub.2264

Cited by 38 publications

(27 citation statements)

References 89 publications

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“…Experimentally, we proposed intracellular signaling pathways to evaluate cell viability mainly by considering PI3K/PKB/Akt upstream stimulus culminating in gene expression related to cell proliferation and survival [ 30 , 31 ]. In addition, as these protein activities are regulated by phosphorylation, the effectivity of this signaling can be measured by the specific phosphorylation profile [ 32 ]. In turn, Akt is a serine/threonine protein kinase that is activated by a number of growth factors and cytokines in an upstream phosphatidylinositol-3 kinase-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

PI3K/AKT signaling drives titanium-induced angiogenic stimulus

Martins

Pinto

Fernandes

et al. 2021

J Mater Sci: Mater Med

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Although osseointegration and clinical success of titanium (Ti)-implanted materials depend on neovascularization in the reactional peri-implant tissue, very little has been achieved considering the Ti-molecules release on the behavior of endothelial cells. To address this issue, we challenged endothelial cells (HUVECs) with Ti-enriched medium obtained from two types of commercial titanium surfaces [presenting or not dual-acid etching (DAE)] up to 72 h to allow molecular machinery analysis. Our data show that the Ti-enriched medium provokes significant stimulus of angiogenesis-related machinery in endothelial cells by upexpressing VEGFR1, VEGFR2, VEGF, eNOS, and iNOS genes, while the PI3K/Akt signaling pathway was also significantly enhanced. As PI3K/AKT signaling was related to angiogenesis in response to vascular endothelial growth factor (VEGF), we addressed the importance of PI3K/Akt upon Ti-enriched medium responses by concomitantly treating the cells with wortmannin, a well-known PI3K inhibitor. Wortmannin suppressed the angiogenic factors, because VEGF, VEGFR1, and eNOS genes were downregulated in those cells, highlighting the importance of PI3K/AKT signaling on driving angiogenic phenotype and angiogenesis performance within the peri-implant tissue reaction. In conjunction, these data reinforce that titanium-implantable devices modify the metabolism of surrounding cells, such as endothelial cells, probably coupling osteogenesis and angiogenesis processes in peri-implant tissue and then contributing to successfully osseointegration of biomedical titanium-based devices.

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Section: Resultsmentioning

confidence: 99%

PI3K/AKT signaling drives titanium-induced angiogenic stimulus

Martins

Pinto

Fernandes

et al. 2021

J Mater Sci: Mater Med

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“…Classically, type III inhibitors displace the c-helix and prevent MEK activation via dual phosphorylation on the TEY motif. There has, however, been an increasing awareness [36][37][38][39][40][41] that type-III kinase binders may induce additional allosteric modification beyond displacement of the C-helix. There also exists the possibility that SC-1-151 may have interactions at other MEK5 allosteric sites, may modify a MEK5 protein/protein interaction, or have activity at a yet uncharacterized protein.…”

Section: Discussionmentioning

confidence: 99%

Constitutive activation of MEK5 promotes a mesenchymal and migratory cell phenotype in triple negative breast cancer

et al. 2021

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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited targeted therapeutic options. A defining feature of TNBC is the propensity to metastasize and acquire resistance to cytotoxic agents. Mitogen activated protein kinase (MAPK) and extracellular regulated kinase (ERK) signaling pathways have integral roles in cancer development and progression. While MEK5/ ERK5 signaling drives mesenchymal and migratory cell phenotypes in breast cancer, the specific mechanisms underlying these actions remain under-characterized. To elucidate the mechanisms through which MEK5 regulates the mesenchymal and migratory phenotype, we generated stably transfected constitutively active MEK5 (MEK5-ca) TNBC cells. Downstream signaling pathways and candidate targets of MEK5-ca cells were based on RNA sequencing and confirmed using qPCR and Western blot analyses. MEK5 activation drove a mesenchymal cell phenotype independent of cell proliferation effects. Transwell migration assays demonstrated MEK5 activation significantly increased breast cancer cell migration. In this study,we provide supporting evidence that MEK5 functions through FRA-1 to regulate the mesenchymal and migratory phenotype in TNBC.

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“…Akt is a protooncogene that regulates various cell functions in tumors, including metabolism, proliferation, survival, migration, and invasion [ 20 ]. The activation of Akt depends on the phosphorylation of threonine (Thr) 308 and serine (Ser) 473 [ 21 ]. mTOR is an atypical serine/threonine kinase which can promote tumor development by regulating cell biological processes such as metabolism, autophagy, and cellular stress [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

FKBP4 Accelerates Malignant Progression of Non-Small-Cell Lung Cancer by Activating the Akt/mTOR Signaling Pathway

Meng

Jiang

et al. 2020

Analytical Cellular Pathology

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Objective. To study the expression, biological function, and mechanism of FKBP4 in non-small-cell lung cancer (NSCLC). Methods. First of all, the expression of FKBP4 in NSCLC tissues and cell lines was detected by qRT-PCR; then, the effects of FKBP4 on proliferation, apoptosis, migration, and invasion of NSCLC were studied by CCK-8 assays, flow cytometry assays, wound-healing assays, and Transwell assays. After that, tumor xenografts were used to explore the effect of FKBP4 on NSCLC tumor growth in vivo, and the phosphorylation of Akt and mTOR was measured by western blot. Results. FKBP4 was highly expressed in NSCLC tissues and cells, and its expression was closely related to NSCLC tumor size, lymph node metastasis, and patient prognosis. In vitro, FKBP4 can promote NSCLC cell proliferation, migration, and invasion and inhibit NSCLC cell apoptosis. In vivo, FKBP4 can promote NSCLC tumor growth. Furthermore, FKBP4 can promote Akt and mTOR phosphorylation and activate the Akt/mTOR signaling pathway and an mTOR inhibitor can neutralize the functions of FKBP4 in NSCLC cells. Conclusion. FKBP4 serves as an oncogene to promote malignant processes in NSCLC, and it has the potential to be used as a biological marker and therapeutic target for NSCLC.

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Control of Akt activity and substrate phosphorylation in cells

Cited by 38 publications

References 89 publications

PI3K/AKT signaling drives titanium-induced angiogenic stimulus

PI3K/AKT signaling drives titanium-induced angiogenic stimulus

Constitutive activation of MEK5 promotes a mesenchymal and migratory cell phenotype in triple negative breast cancer

FKBP4 Accelerates Malignant Progression of Non-Small-Cell Lung Cancer by Activating the Akt/mTOR Signaling Pathway

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