Search results for "protein phosphorylation"

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

2011

Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described …

Fos-related antigen 2 (Fra-2) memorizes photoperiod in the rat pineal gland

2004

As the physiological role of fos-related antigen-2 (Fra-2) is largely unknown and since the pineal plays an important role in the photoperiodic control of the body, we have tested the hypothesis that Fra-2 expression is photoperiod-dependent and may be involved in imprinting photoperiod on the pineal gland and the body as a whole. To this end, we have investigated Fra-2 mRNA expression and Fra-2 protein expression under various light/dark (LD) cycles. A clear nocturnal increase occurs for both monitored parameters under all photoperiodic conditions studied. The level of Fra-2 protein expression clearly depends on photoperiod, because the amount of protein at dark onset and during the night …

Deficient p27 Phosphorylation at Serine 10 Increases Macrophage Foam Cell Formation and Aggravates Atherosclerosis Through a Proliferation-Independen…

2011

OBJECTIVE: Genetic ablation of the growth suppressor p27(Kip1) (p27) in the mouse aggravates atherosclerosis coinciding with enhanced arterial cell proliferation. However, it is unknown whether molecular mechanisms that limit p27's protective function contribute to atherosclerosis development and whether p27 exerts proliferation-independent activities in the arterial wall. This study aims to provide insight into both questions by investigating the role in atherosclerosis of p27 phosphorylation at serine 10 (p27-phospho-Ser10), a major posttranslational modification of this protein. METHODS AND RESULTS: Immunoblotting studies revealed a marked reduction in p27-phospho-Ser10 in atheroscleroti…

2020

The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a nov…

Modulation of mutagenicity by phosphorylation of mutagen-metabolizing enzymes.

2004

In this Minireview, we discuss our findings on phosphorylation of cytochromes P450 (CYP) and influence of this modification on metabolic toxification and/or detoxification of a variety of mutagens. We show that phosphorylation drastically interferes with the mutagenicity of several classes of compounds which are of high human relevance (cytostatic drugs of the cyclophosphamide type, aromatic amines/amides, and nitrosamines). We illustrate this by describing the consequences of the stimulation of protein kinase A (with the example of CYP2B1 and CYP2E1), stimulation of protein kinase C, and inhibition of protein phosphatases PP1 and PP2A (with the example of CYP1A1 and CYP1A2). We discuss a p…

Analysis of phosphorylation-dependent modulation of Kv1.1 potassium channels.

2003

The voltage-gated potassium channel Kv1.1 contains phosphorylation sites for protein kinase A (PKA) and protein kinase C (PKC). To study Kv1.1 protein expression and cellular distribution in regard to its level of phosphorylation, the effects of PKA and PKC activation on Kv1.1 were investigated in HEK 293 cells stably transfected with Kv1.1 (HEK 293/1). Without kinase activation, HEK 293/1 cells carry unphosphorylated Kv1.1 protein in the plasma membranes, whereas large amounts of phosphorylated and unphosphorylated Kv1.1 protein were located intracellularly. Activation of PKA resulted in phosphorylation of intracellular Kv1.1 protein, followed by a rapid translocation of Kv1.1 into the pla…

Early signaling network in tobacco cells elicited with methyl jasmonate and cyclodextrins.

2012

We analyze, for the first time, the early signal transduction pathways triggered by methyl jasmonate (MJ) and cyclodextrins (CDs) in tobacco (Nicotiana tabacum) cell cultures, paying particular attention to changes in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)), the production of hydrogen peroxide (H(2)O(2)) and nitric oxide (NO), and late events like the induction of capsidiol. Our data indicate that MJ and CDs trigger a [Ca(2+)](cyt) rise promoted by Ca(2+) influx through Ca(2+)-permeable channels. The joint presence of MJ and CDs provokes a first increase in [Ca(2+)](cyt) similar to that observed in MJ-treated cells, followed by a second peak similar to that found in the presence…

Molecular characterization and evolution of the protein phosphatase 2A B' regulatory subunit family in plants.

2002

Abstract Type 2A serine/threonine protein phosphatases (PP2A) are important components in the reversible protein phosphorylation events in plants and other organisms. PP2A proteins are oligomeric complexes constituted by a catalytic subunit and several regulatory subunits that modulate the activity of these phosphatases. The analysis of the complete genome of Arabidopsis allowed us to characterize four novel genes, AtB′ε, AtB′ζ,AtB′η, and AtB′θ, belonging to the PP2A B′ regulatory subunit family. Because four genes of this type had been described previously, this family is composed of eight members. Reverse transcriptase-polymerase chain reaction experiments showed thatAtB′ε mRNAs are prese…

Investigation of cancer drug resistance mechanisms by phosphoproteomics

2020

Abstract Cancer cell mutations can be identified by genomic and transcriptomic techniques. However, they are not sufficient to understand the full complexity of cancer heterogeneity. Analyses of proteins expressed in cancers and their modification profiles show how these mutations could be translated at the functional level. Protein phosphorylation is a major post-translational modification critical for regulating several cellular functions. The covalent addition of phosphate groups to serine, threonine, and tyrosine is catalyzed by protein kinases. Over the past years, kinases were strongly associated with cancer, thus inhibition of protein kinases emanated as novel cancer treatment. Howev…

Plant protein phosphorylation monitored by capillary liquid chromatography–element mass spectrometry

2007

Abstract Many essential cellular functions such as growth rate, motility, and metabolic activity are linked to reversible protein phosphorylation, since they are controlled by signaling cascades based mainly on phosphorylation/dephosphorylation events. Quantification of global or site-specific protein phosphorylation is not straightforward with standard proteomic techniques. The coupling of capillary liquid chromatography (μLC) with ICP-MS (inductively coupled plasma-mass spectrometry) is a method which allows a quantitative screening of protein extracts for their phosphorus and sulfur content, and thus provides access to the protein phosphorylation degree. In extension of a recent pilot st…