Modulation of protein phosphorylation

Weber TJ, Ou X, Hart C, et al. 1991c. Modulation of protein phosphorylation in rat aortic smooth muscle cells by 2,3,7,8-tetrachlorodibnezo-p-dioxin (TCDD) in vivo [Abstract 1335], Toxicologist 11 340. 

Okadaic acid and its analogues DTX-1 and DTX-2 are specific inhibitors of serine/threonine protein phosphatases 1 and 2A, two enzymes involved in the regulation of many cellular processes by modulation of proteins phosphorylation/dephosphorylation degree. ... 

Sugimoto I, Hashimoto E. 2006. Modulation of protein phosphorylation by Mr 25,000 protein partially overlapping phosvitin and hpwviteUtn 2 in Xenopus laevis vitellogenin B1 protein. Protein J 25(2) 109-115. 

Phosphorylation is a common method of regulation. As described above, SH2 domains bind to phosphorylated tyrosine residues. Conversely, phosphorylation of serines and threonines proximal to SH3 and PDZ domains uncouples them from their target motifs. Therefore modulation of protein kinase activity in cells regulates interactions between adaptor proteins and their target proteins. 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Phosphorylation on serine, threonine, and tyrosine residues is an extremely important modulator of protein function. Phosphorylation can be analyzed by mass spectrometry with enrichment of compounds of interest using immobilized metal affinity chromatography and chemical tagging techniques, detection of phosphopep-tides using mass mapping and precursor ion scans, localization of phosphorylation sites by peptide sequencing, and quantitation of phosphorylation by the introduction of mass tags (McLachlin and Chait 2001). 

Isfort RJ, Cody DB, Asuith TN, Ridder GM, Stuard SB, LeBoeuf RA. 1993. Induction of protein phosphorylation, protein synthesis, immediate-early-gene expression and cellular proliferation by intracellular pH modulation. Eur. J. Biochem. 213 349—57... 

Linden, L. and Kreimer, G. (1995) Calcium modulates rapid protein phosphorylation/ dephosphorylation in isolated eyespot apparatuses of the green alga Spermatozopsis similis. Planta 197, 343-351. 

Mitogen activated protein kinase (MARK) cascades are three kinase modules activated by phosphorylation. The three kinase modules are composed of a MAPK, a MAPKK, and a MAPKKK. There are multiple members of each component of the MAPK cascade that are conserved from yeast to human. Activation of selective MAPK modules by specific stimuli regulates cell functions such as gene expression, adhesion, migration, differ entiation, and apoptosis. 

The transcriptional activity of NRs is also modulated by various posttranslational modifications of the receptors themselves or of their coregulatory proteins. Phosphorylation, as well as several other types of modification, such as acetylation, SUMOylation, ubiquitinylation, and methylation, has been reported to modulate the functions of NRs, potentially constituting an important cellular integration mechanism. In addition to the modifications of the receptors themselves, such modifications have been reported for their coactivators and corepressors. Therefore, these different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. 

Hyperphosphorylation of ERAK-1 by itself and ERAK-4 causes ERAK-1 to dissociate from the membrane-bound complex. Tumour necrosis factor (TNF) receptor-associated factor-6 ( TRAF-6), a cytoplasmic protein, is activated by ERAK-1 and with TAB-2, another cytoplasmic protein, activates transforming growth factor-P (TFG-P)-activating kinase (TAK-1). During this process both TRAF-6 and TAK-1 become ubiquitinated. TAK-1 then promotes activation of the IkB kinases, or the IKK family, EKKa and EKK 3 (found in a complex with NFicB-essential modulator [NEMO]), which phosphorylate the IkB family, notably IkB-u. IkB-u is an inhibitor of NFkB as it sequesters NFkB in an... 

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

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