Proteins phosphorylation and

The dopamine is then concentrated in storage vesicles via an ATP-dependent process. Here the rate-limiting step appears not to be precursor uptake, under normal conditions, but tyrosine hydroxylase activity. This is regulated by protein phosphorylation and by de novo enzyme synthesis. The enzyme requites oxygen, ferrous iron, and tetrahydrobiopterin (BH. The enzymatic conversion of the precursor to the active agent and its subsequent storage in a vesicle are energy-dependent processes. 

L-type Ca channels are primarily regulated by voltage and are thus opened and closed in response to changes in membrane potential, but in addition, they are regulated by receptor-dependent processes involving protein phosphorylation and G-proteins (Fig. 2). Many lines of evidence support the hypothesis that Ca channels are regulated by phosphorylation by several protein kinases, in particular by... 

Clarke, P. R., and Karsenti, K. (1991). Regulation of p34cprotein kinase new insights into protein phosphorylation and the cell cycle. J. Cell Sci. 100 409-414. 

When glucagon levels fall, cAMP phosphodiesterase destroys the accumulated cAMP, and specific protein phosphatases remove the phosphate from the phosphoproteins. These phosphatases themselves are often regulated by phosphorylation—yes, there are phosphatase kinases and phosphatase phosphatases. It s really easy to lose it here, but the key factor is that increased glucagon levels lead to increased protein phosphorylation, and decreased glucagon levels lead to decreased protein phosphorylation. 

Calmodulin, a calcium binding protein, is involved in Ca2+-dependent regulation of several synaptic functions of the brain synthesis, uptake and release of neurotransmitters, protein phosphorylation and Ca+2 transport. It reacts with TET, TMT and TBT which then inactivates enzymes like Ca+2-ATPase and phosphodiesterase. In vitro studies indicated TBT was greater at inhibiting calmodulin activity than TET and TMT, whereas in vivo the order was TET > TMT > TBT. This may be due to the greater detoxification of TBT (66%) in the liver before moving to other organs30,31. 

Hunter, T. Protein kinases and phosphatases the yin and yang of protein phosphorylation and signaling. Cell 80 225-236,1995. 

Turner, K. M., Burgoyne, R. D. and Morgan, A. Protein phosphorylation and the regulation of synaptic membrane traffic. Trends Neurosci. 22 459-464,1999. 

The immunotoxicology of metals in fishes has been reviewed elsewhere [74-76, 45], Overall, the immune systems of fishes are highly sensitive to metals, although the effects are not always suppression of immune functions. Burnett [76] demonstrated that low levels of metals increased intracellular calcium, increased protein phosphorylation, and stimulated lymphocyte proliferation in fish. Since most metals are toxic to both the nervous system and the immune system, a neuroendocrine-immune link to immuno-toxicity from metal exposure is likely. 

Other PTMs may involve changes in the chemical nature of amino acids (e.g., citrullination or deimination). Because many of these modifications result in mass changes that are measurable by MS, they are amenable to detection by MS-based approaches. A number of emerging MS-based strategies allow the identification of PTMs. Several MS-based methods to determine the types and sites of protein phosphorylation and ubiquitination have been developed. Phosphorylation occurs mainly on serine, threonine, and tyrosine residues at a frequency ratio of 1800 200 1 in vertebrates.70 Although the phosphorylation of tyrosine residues occurs less frequently in the proteome, it has been extensively studied. 

Haystead, T.A., et al.. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature, 337, 6202, 78, 1989. 

Kwiatkowska-Patzer B, Domanska-Janik K (1991) Increased 19 kDa protein phosphorylation and protein kinase C activity in pressure-overload cariac hypertrophy. Basic Res Cardiol 86 402-409... 

Shimizu E, Zhao MR, Nakanishi H, Yamamoto A, Yoshida S, Takada M, Ogura T, Sone S (1996) Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines. Oncology 53 494-504... 

Jayashree, T., Praveen-Rao, J., and Subramanyam, C. (2000). Regulation of aflatoxin production by Ca2- -/calmodulin-dependent protein phosphorylation and dephosphorylation. FEMS Microbiol. Lett. 83, 215-219. 

Sassone-Corsi Is the protein phosphorylated, and does this change in the cycle ... 

The regulation of translation is accomplished in this system via a specific inhibitory protein and an initiation factor of translation. The binding activity of the inhibitor protein is regulated by protein phosphorylation, and thus, by protein kinases. The activity of protein kinases can be regulated in a multitude of ways. A signal initiating from insulin, for example, can activate the PI3-kinase and the Akt kinase pathway (see 6.6.2), resulting in phosphorylation of 4E-BP1. 

Stimulation of NO synthase leads to activation of a NO-sensitive guanylyl cyclase. The associated increase in the cGMP level has multiple consequences. The cGMP can stimulate cGMP-dependent protein kinases it can also open cGMP-controUed ion channels. As a consequence, an increase in the intracellular Ca concentration takes place and a Ca signal is produced. NO can influence both protein phosphorylation and InsPs/diacylglycerol and Ca metabolism by this mechanism and activate a broad palette of biochemical reactions in the cell. 

Our results demonstrated that the identified subsets of the activated protein kinases significantly increased the accuracy of clinical outcome predictions. Most notably in the study, we evaluated protein phosphorylation levels instead of total protein expression levels. Protein phosphorylation and dephosphorylation are well-characterized biochemical processes for protein kinases to conduct cellular signal transduction. Phosphorylation at certain tyrosine, serine, or threonine residues in kinases is a key step for their activation, and the measurement of these phosphorylations reflects their functional status in vivo. Thus, the protein kinase phosphorylation-based tissue microarray more accurately reveals the molecular mechanisms of breast cancers, and more accurately predicts the individualized survival and treatment response. 

Erythropoietin stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors. The erythropoietin receptor is a member of the JAK/STAT superfamily of cytokine receptors that use protein phosphorylation and transcription factor activation to regulate cellular function (see Chapter 2). Erythropoietin also induces release of reticulocytes from the bone marrow. Endogenous erythropoietin is primarily produced in the kidney. In response to tissue hypoxia, more erythropoietin is produced through an increased rate of transcription of the... 

FIGURE 15-14 Protein phosphorylation and dephosphorylation. Protein kinases transfer a phosphoryl group from ATP to a Ser, Thr, or Tyr residue in a protein. Protein phosphatases remove the phosphoryl group as P . 

Barford, D. (1999) Structural studies of reversible protein phosphorylation and protein phosphatases. Biochem. Soc. Trans. 27, 751-766. 

Proud, C. G., Guanine nucleotides, protein phosphorylation and control of translation. Trends Biochem. Sci. 11 73-77,... 

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