Proteins, phosphorylated

Newton AC (2003) Regulation of the ABC kinases by phosphorylation protein kinase C as a paradigm. Biochem 1370 361-371... 

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. 

Mammalian proteins are the targets of a wide range of covalent modification processes. Modifications such as glycosylation, hydroxylation, and fatty acid acylation introduce new structural features into newly synthesized proteins that tend to persist for the lifetime of the protein. Among the covalent modifications that regulate protein function (eg, methylation, adenylylation), the most common by far is phosphorylation-dephos-phorylation. Protein kinases phosphorylate proteins by... 

Disorders of mitochondrial oxidative phosphorylation Proteins encoded by mitochondrial genes Proteins encoded by nuclear genes... 

The existence of the Ei, and E2 states of the phosphorylated protein, i.e., the high-and low-energy phosphoenzyme intermediate, has been demonstrated by the ATP ADP exchange reaction [92,93] and by the exchange between inorganic phosphate and water [94]. 

The endothelin B receptor is an example of characterization of a homogeneous, affinity purified protein (Roos et al., 1998). Significant progress has been made in the development of techniques for more high-throughput identification of phosphorlyation events. Analysis of large sets of phosphorylated proteins is facilitated by the availability of affinity purification methods such as anti-phosphotyrosine or anti-phosphoserine antibodies or metal affinity chromatography (Neubauer and Mann, 1999 Soskic et al., 1999). These methods are not specific to a particular protein but rather are used to fractionate all proteins that are phosphorylated. 

Volume 201. Protein Phosphorylation (Part B Analysis of Protein Phosphorylation, Protein Kinase Inhibitors, and Protein Phosphatases)... 

MK2 (also termed MAP kinase-activated protein kinase 2, MAPKAP-K2) is activated by p38 MAP kinase a// (Kotlyarov et al, 2002 Roux and Blenis, 2004). MK2 plays a key role in the control of the production of certain cytokines, for example, tumor necrosis factor a. MK2 does so by phosphorylating proteins that bind specifically to the regulatory regions in the S untranslated regions (UTRs) of such mRNAs (Hitti et al, 2006). These regions contain AU-rich elements (AREs) to which proteins such as HnRNP A1 also bind. 

Tyrosine kinases phosphorylate protein tyrosine residues using ATP. Phospholipase C cleaves PIP2 into IP3 and PAG. 

L The answer is a. (Hardman, pp 1460, 14642) Cosyntropin is related to adrenocorticotropin. It corresponds to the first 24 amino acids of adreno-corticotropin. Cosyntropin complexes with a plasma membrane receptor that brings about the activation of adenylyl cyclase. Adenylyl cyclase catalyzes the formation of cAMP from ATP In the cytoplasm, cAMP activates cAMP-dependent protein kinase, which participates in the phosphorylation of specific substrate proteins (e.g., enzymes). The phosphorylated protein eventually induces the particular response on the target cell. 

Since then, a plethora of tyrosine-phosphorylated proteins has been discovered. Originally, tyrosine phosphorylation was believed to be involved primarily in regulating cell proliferation, since many oncogene products and growth factor receptors are protein tyrosine kinases (PTKs). However, it has become clear that tyrosine phosphorylation is involved in regulating a variety of cellular processes. In fact, the nervous system contains a large variety of PTKs and protein tyrosine phosphatases (PTPs), and some of these are exclusively expressed in neuronal tissues. Figure 24-1 shows the... 

FIGURE 24-1 Phosphotyrosine staining of a hippocampal neuron. A cultured rat hippocampal pyramidal neuron is stained with an antiphosphotyrosine antibody and detected by a secondary antibody conjugated to rhodamine. The staining reflects the presence of tyrosine-phosphorylated proteins throughout the neuron, including the cell body and synaptic regions. 

Moon, I. S., Apperson, M. L. and Kennedy, M. B. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc. Natl Acad. Sci. U.S.A. 91 3954-3958,1994. 

Figure 4.20 (b) those receptors which recruit cytosolic TK receptors for growth hormone, erythropoietin (EPO), Prolactin. Binding of hormone, for example leptin, causes dimerisation of the receptor and attachment of cytosolic TK which phosphorylate protein substrate(s)... 

Most frequently, extracts of either prokaryotic or eukaryotic origin as such from Escherichia coli, wheat germ or rabbit reticulocytes are employed for cost reasons and availability. While those based on E. coli are unable of post-translational protein modification, eukaryotic extracts do allow synthesis of glycosylated or phosphorylated proteins to some extent when additional components, such as microsomes for glycosylation are added. Care needs to be taken with cell-free systems recombinated from the individual components when a native protein is to be produced that does not fold spontaneously... 

McLachlin D.T. and Chait B.T. (2001), Analysis of phosphorylated proteins and peptides by mass spectrometry, Curr. Opin. Chem. Biol. 5(5), 591-602. 

Saxton, T.M., Oostween, I., BowteU, D., Aebersold R., and Gold, M.R., 1994, B cell antigen receptor crosshnking induces phosphorylation of the ras activators SHC and mSOSl as well as the assembly of complexes containing SHC, Grb2 and SOSl and a 145 kDa tyrosine phosphorylated protein. J. Immunol. 153 623-636. 

Smit, L., de Vries-Smits, A.M.M., Bos, J.L., and Borst, J., 1994, B cell antigen receptor stimulation induces formation ofaShc-Grb2 complex containing multiple tyrosine-phosphorylated proteins. 7. Biol. Chem. 269 20209-20212... 

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