OBJECTIVE Vascular smooth muscle cell (VSMC) apoptosis occurs at low levels in atherosclerotic plaques and in vessel remodeling; however, the consequences and mediators of these levels are not known. Akt1 protects against VSMC apoptosis largely through inactivating target proteins such as forkhead class O transcription factor 3a (FoxO3a), but Akt1 signaling is reduced and FoxO3a activity is inc...

Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their pre...

Pre-TCR signals regulate the transition of the double-negative (DN) 3 thymocytes to the DN4, and subsequently to the double-positive (DP) stage. In this study, we show that pre-TCR signals activate Akt and that pharmacological inhibition of the PI3K/Akt pathway, or combined ablation of Akt1 and Akt2, and to a lesser extent Akt1 and Akt3, interfere with the differentiation of DN3 and the accumul...

Strategies to address resistance to platin drugs are greatly needed in human epithelial cancers (e.g., ovarian, head/neck, and lung) where platins are used widely and resistance occurs commonly. We found that upon DNp63a overexpression, AKT1 and phospho-AKT1 levels are upregulated in cancer cells. Investigations using gel-shift, chromatin immunoprecipitation and functional reporter assays impli...

Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice,...

Mitochondrial respiratory stress (also called mitochondrial retrograde signaling) activates a Ca(2+)/calcineurin-mediated signal that culminates in transcription activation/repression of a large number of nuclear genes. This signal is propagated through activation of the regulatory proteins NFκB c-Rel/p50, C/EBPδ, CREB, and NFAT. Additionally, the heterogeneous ribonucleoprotein A2 (hnRNPA2) fu...

IFN-β is a critical antiviral cytokine that is capable of modulating the systemic immune response. The transcriptional induction of IFN-β is a highly regulated process, involving the activation of pattern recognition receptors and their downstream signaling pathways. The Akt family of serine/threonine kinases includes three isoforms. The specific role for the individual Akt isoforms in pattern ...

Background It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). In contrast, little is known about the effects of increasing skeletal muscle mass, typically achieved through resistance training, on this process. Here, we utilized transgenic (TG) mice, that can induce the growth of functional skeletal muscle by switchi...

Potassium (K(+)) is an essential nutrient for plant growth and development. Plants often adapt to low K(+) conditions by increasing their K(+) uptake capability. Recent studies have led to the identification of a calcium signaling pathway that enables plants to act in this capacity. Calcium is linked to two calcineurin B-like calcium sensors (CBLs) and a target kinase (CBL-interacting protein k...