Phosphorylation cellular signals

In contrast to tyrosine kinases, Tyrosine phosphatases (PTPs) are enzymes which act on phosphorylated proteins and catalyze the transfer of a phosphate group from a tyrosine residue to a water molecule, generating orthophosphates in a process which is referred to as dephosphorylation. PTPs are involved in many cellular signal transduction pathways. 

Cellular signals converge at the level of protein phosphorylation pathways 410... 

Cellular signals converge at the level of protein phosphorylation pathways. Individual intracellular messenger pathways, such as cAMP, Ca2+ and MAPK pathways, are often drawn as distinct biochemical cascades that operate in parallel in the control of cell function. While this is useful for didactic purposes, it is now well established that these various pathways function as complex webs, with virtually every conceivable type of interaction seen among them. 

Wu RC, Qin J, Yi P, Wong J, Tsai SY, Tsai M J, O Malley BW (2004) Selective phosphorylations of the SRC-31AIB 1 coactivator integrate genomic reponses to multiple cellular signaling pathways. Mol Cell 15 937-949... 

A completely different type of effect is observed in metabotropic receptors (bottom right). After binding of the transmitter, these interact on the inside of the postsynaptic membrane with Gproteins (see p. 384), which in turn activate or inhibit the synthesis of second messengers. Finally, second messengers activate or inhibit protein kinases, which phosphorylate cellular proteins and thereby alter the behavior of the postsynaptic cells (signal transduction see p.386). 

Any of a broad class of phosphoryl-transfer enzymes [EC 2.7.1.x] that catalyze the ATP-dependent phosphorylation of proteins, most often occurring at seryl, threo-nyl, and tyrosyl residues. These enzymes are central participants in cellular signal transduction pathways, and their discovery and recognition as primary control components of the cell culminated in the award of the 1992 Nobel Prize in Medicine and Physiology to American enzymologists Edwin Krebs and Edward Fischer. There is reason to believe that approximately 2% of the coding sequences in the human genome specify some 2000 different kinases that phosphorylate protein substrates. The prototypical enzyme is known as 3, 5 -cAMP-stimulated protein kinase (or, protein kinase A). See specific protein kinase... 

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. 

Cai H, Li Z, Davis ME, Kanner W, Harrison DG, Dudley SC. Jr 2003. Akt dependent phosphorylation of serine 1179 and mitogen-activated protein kinase kinase/extra-cellular signal-regulated kinase 1/2 cooperatively mediate activation of the endothelial nitric-oxide synthase by hydrogen peroxide. Mol Pharmacol 63 325-331. 

Zhang, L., Ma, Y., Zhang, J., et al. 2005b. A new cellular signaling mechanism for angiotensin II activation of NF-kappaB An IkappaB-independent, RSK-mediated phosphorylation of p65. Arterioscler Thromb Vase Biol 25 1148-1153. 

Reversible chemical modification of enzymes, which was discovered in 1955 by Edmond Fischer and Edwin Krebs [58], is a more prevalent mechanism for cellular signaling switching. Fischer and Krebs showed that enzymes can be turned from an inactive form to an active form via phosphorylation of certain residues of the protein. Enzymes that catalyze phosphorylation (addition of a phosphate group coupled with ATP or GTP hydrolysis) are called protein kinases. Enzymes that catalyze dephosphorylation (which is not the reverse reaction of the phosphorylation) are called phosphatases. For example, a protein tyrosine phosphatase is an enzyme that catalyzes the removal of a phosphate group from a tyrosine residue in a phosphorylated protein [57],... 

Recently, several studies suggested that protein nitration could be a cellular signaling mechanism and is often a reversible and selective process, similar to protein phosphorylation (Aulak et al., 2004 Koeck et al., 2004). In addition, modified proteins are believed to be either degraded or subject to processes that could lead to enzymatic denitration (Gow et al., 1996 Kamisaki et al., 1998 Me et al., 2003). The latter possibility is intriguing because this would allow the process of tyrosine nitration to be reversible and thus enable a more dynamic physiological role. Protein nitration is observed under normal conditions in all tissues. In AD brain levels of nitrated proteins were found to be increased compared to that of control (Smith et al.. 

Ras is the master controller of a central cellular signalling pathway, the MAP kinase-phosphorylation cascade. Ras accomplishes its regulatory role in a way that is different from the function of the other regulatory components of signalling networks discussed up to now. Ras is a GTPase. In the GTP-bound state its activity is switched on and in the GDP-bound state, switched off. 

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