Serin phosphorylation

There are up to 3 serine phosphorylation sites per subunit, but for simplicity only one site per unit shown is in this figure. 

In cells of the mammary gland, either in normal epithelial or in cancerous cells, the packaging of chromosomal DNA into chromatin restricts the access of the transcription machinery, thereby causing transcriptional repression. The basic N-termini of histones are subject to post-translational modifications, including lysine acetylation, lysine and arginine methylation, serine phosphorylation and ubiquitinylation [56]. It has been proposed in the histone code hypothesis that the intricate pattern of modifications of the N-terminal histone tail influences gene regulation [57]. 

ZhaJ, HaradaH, YangE, etal. Serine phosphorylation of death agonist Bad in response to survival factor results in binding to 14-3-3 not Bcl-X(L). Cell 1996 87(4) 619-628. 

K. Morino, K. F. Petersen, S. Dufour, D. Befroy, J. Frattini, N. Shatzkes, S. Neschen, M. F. White, S. Bilz, S. Sono, M. Pypaert and G. 1. Shulman, Reduced mitochondrial density and increased lRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. /. Clin. Invest., 2005,115,3587-3593. 

The steroid hormone receptors are phophoproteins which are usually phosphorylated on several positions. The phosphorylation sites are mainly foimd in the N-terminal region of the receptors. Serine phosphorylation prevails. One rare example of tyrosine phosphorylation is described for the case of estrogen receptors. The consequences of phosphorylation for the receptor proteins are varied. It is conceivable, and in some cases experimentally proven, that it has influence on hormone binding, nuclear transport, DNA binding and transactivation. 

Paxton WG, Marrero MB, Klein ID, Delafontaine P, Berk BC, Bernstein KE (1994) The angiotensin II ATI receptor is tyrosine and serine phosphorylated and can serve as a substrate for the src family of tyrosine kinases. Biochem Biophys Res Commun 200(l) 260-267... 

Ellerbroek SM, Wennerberg K, Burridge K (2003) Serine phosphorylation negatively regulates RhoA in vivo. J Biol Chem 278 19023-31... 

Ser-228 in GXSXG lipase consensus sequence, CaLB domain, responsive to PIP2 for catalytic activity and membrane association, multiple serine phosphorylation sites... 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

One problem associated with the yeast 2-hybrid system is that protein interactions that are dependent on posttranslational modifications that can occur only in mammalian cells, would not be detected. For example, monoubiquitinylation and serine phosphorylation of a Fanconi anemia complementation group D2 protein (FANC-D2) are both required for mediating cellular resistance to ionizing radiation (122), an interaction that would be missed using this approach. 

Folh, F., Kahn, C. R., Hansen, H., et al. 1997. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in in-sulin/angiotensin II crosstalk. J Clin Invest 100 2158-2169. 

In intact cells insulin has been shown to stimulate receptor autophosphorylation. However, much smaller amounts of phosphotyrosine were found compared to that seen using purified, solubilized receptor preparations and, indeed, the predominant phosphorylation actually occurred on serine residues [69,71]. It has been suggested that there may be an insulin-stimulated, phosphoseryl-specific kinase which is loosely associated with the receptor and is activated by the receptor tyrosyl kinase [61]. This might account for the insulin-stimulated phosphoseryl kinase activity observed in both intact cells and when using crude, solubilized receptor preparations. Such an activity might also provide a mechanism for insulin s ability to enhance serine phosphorylation on target proteins in plasma membranes and elsewhere in the cell [25,78]. Nevertheless, (auto)-phosphorylation of the insulin receptor on tyrosine residues has been shown to occur immediately upon receptor occupancy by insulin and to precede any phosphorylation on serine residues [69]. Indeed, it remains to be seen as to whether the seryl phosphorylation occurs as a direct insulin-stimulation event or mediated by other kinases (cAMP/C-kinase) as a consequence of insulin-stimulated autophosphorylation on tyrosyl residues. 

Takada Y, Mukhopadhyay A, Kundu GC, Mahabeleshwar GH, Singh S (2003) Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65 evidencefortheinvolvement of I kappa B alpha kinase and Syk protein-tyro sine kinase. J Biol Chem 278 24233-24241... 

Z. Wen, Z. Zhong, and J. E. Darnell Jr. Maximal activation of transcription by Statl and Stat3 requires both tyrosine and serine phosphorylation. Cell, 82 (2), 241-250, 1995. 

An interesting observation was made when VPl and the minor structural protein VP2 were coexpressed in insect cells. First, immunoprecipitation analyses demonstrated a physical association between VPl and VP2, which was not surprising given the incorporation of small amounts of this protein into native virions. Second, and more interesting, the phosphorylation pattern of VPl changed in the presence of VP2. When expressed in insect cells, VPl is phosphorylated predominantly on serine, whereas in virus-infected mouse cells there is a 2 1 phosphothreonine phosphoserine ratio. On coexpression of VP2, the nonphysiologic serine phosphorylation was reduced and phosphorylation of Thr-63, the same residue that is phosphorylated in infected mouse cells, was detected (Li et al., 1995). Thus, coexpression of the two proteins in insect cells led to proper substrate phosphorylation. 

Missense substitutions at Raf serine phosphorylation sites with charged amino acids to mimic persistent phosphorylation. 

Hatfield DL, Gladyshev VN. How selenium has altered our understanding of the genetic code. Mol. CeU. Biol. 2002 22 3565-3576. Wu XQ, Gross HJ. The length and the secondary structure of the D-stem of human selenocysteine tRNA are the major identity determinants for serine phosphorylation. EMBO J. 1994 13 241-248. Hubert N, Sturchler C, Westhof E, Carbon P, Krol A. The 9/4 secondary structure of eukaryotic selenocysteine tRNA more pieces of evidence. Rna 1998 4 1029-1033. 

Moger J, Gribbon AP, Sewing A, Winlove MG (2007) Feasibility study using surface-enhanced Raman spectroscopy for the quantitative detection of tyrosine and serine phosphorylation. Biochim Biophys Acta 1770(6) 912-918... 

Structural Insights, Glycogen Phosphorylase, looks closely at the structural mechanisms of phosphorylase regulation, examining the efects of allosteric effectors and serine phosphorylation. 

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