Phosphorylation, of casein

Matheis, G., Penner, H.M., Feeney, R.E., and Whitaker, J.R. 1983. Phosphorylation of casein and lysozyme by phosphorus oxychloride. J. Agric. Food Chem. 31, 379-387. 

Mercier, J.-C. 1981. Phosphorylation of caseins, present evidence for an amino acid triplet code postranslationally recognised by specific kinases. Biochimie 63, 1-17. 

Using casein as substrate, cyclic AMP has been measured directly in crude tissue extracts by the stimulation of the rate of phosphorylation of casein catalysed by skeletal muscle protein kinase [158]. By using high concentrations of casein and [y- P]ATP, the interference with the protein kinase activity by materials present in the tissue extracts is minimised and preliminary purification is not necessary. The phosphory-lated casein is isolated on filter paper discs. As little as 0.5 pmol of cyclic AMP can be measured. The assay is rapid and simple. 

Caserns have natural ester-bound phosphate and this gives caseins some of their unique properties. Whey proteins do not naturally contain phosphate ester groups. Studies have shown that the phosphorylation of caseins and whey proteins creates novel functionality in these proteins. 

ATP + protein tyrosine <116, 120, 123> (<116>, autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein [329] <120>, pl35tyk2 tyrosine kinase directly binds and tyrosine phosphorylates a subunit of the type IIFN receptor, IFN-R [341] <123>, specifically phosphorylates Tyr527 of p60c-src from neonatal rat brain, specifically phosphorylates a negative regulatory site of p60c-src [346]) (Reversibility <116, 120, 123> [329, 341, 346]) [329, 341, 346]... 

HSFl phosphorylation must be sensitive to nonheat inducers of HSF-DNA binding activity because HSFl phosphorylation can be achieved at 37 °C by other inducers of the HS response. HSF 1 contains polypeptide sequences that could serve as substrates for well characterized protein kinases, but few of these are known to be heat inducible. One family of protein kinases, the S6 protein kinases, have already been shown to exhibit heat inducible activity however, their peak level of activity during HS occurs well after the maximal induction of HSF phosphorylation (Jurivich et al., 1991). Thus, other protein kinases are likely to be directly linked to the phosphorylation of HSF. Some of the putative protein phosphorylation sites on HSF include motifs for protein kinase C, casein kinase, and enterokinase. There are tyrosine sequences that match substrates for known tyrosine kinases, but whether these residues are accessible to phosphorylation is not established. 

Casein-derived phosphorylated peptides are believed to enhance the bioavailability of calcium from milk and dairy products (Pihlanto and Korhonen, 2003), and a phosphopeptide derived from (3-casein has been shown to increase iron bioavailability (Bouhallab et ah, 2002 Peres, 1999). Other casein-derived peptides have been found to contain antihypertensive activity in rats (Leclerc et ah, 2002 Miguel et ah, 2009). A number of casein fragments demonstrate antibacterial activity (Kilara and Panyam, 2003). 

Activation of cells results in the release of IKB, followed by the rapid proteolysis of IKB. Although phosphorylation of serine 32 and 36 in the amino-terminal part of IKBa occurs when the proinflammatory cytokines or mitogens are administered to a T lymphocytic cell line, a different site of action has been found after H2O2 incubation (Schoonbroodt et al., 2000). The tyrosine residue 42 and the C-terminal PEST (Pro-Glu-Ser-Thr) domain plays a major role in the phosphorlylation of IKB after treatment with H2O2. Furthermore the CVinducible phosphorylation was not dependent upon IKB kinase activation but involved casein kinase II. The importance of iron for the activation of NFKB was underlined by the fact that... 

According to previous analyses of these paintings, the colour layers contain a high concentration of phosphorus (in the order of units of per cent) [40] this led restorers to the assumption that they contain casein which was ruled out by our detailed analysis. Thus, a high concentration of phosphorus coming from the proteinaceous binder is excluded because of the low concentration of phosphorus in the most phosphorylated binder (casein, max. 5% phosphoms) and the amount in the colour layer (up to 10%).The source of phosphorus was discovered by powder X-ray microdifffaction it comes from aluminium phosphate that was probably used as a substrate for the precipitation of red organic lake [40],... 

Wisniewski, J.R., Szewczuk, Z., Petry, I., Schwanbeck, R., and Renner, U. (1999) Constitutive phosphorylation of the acidic tails of the high mobility group 1 proteins by casein kinase II alters their conformation, stability, and DNA binding specificity. J Biol. Chem. 274, 20116-20122. 

There is growing evidence that clock proteins are regulated dynamically in both temporal (production and degradation) and spatial (nuclear and cytoplasmic) dimensions. The phosphorylation of mPERl and mPER2 by casein kinase le (CKIe) is known as an important step for the accumulation of negatively active clock proteins (Lowrey et al 2000) as in Drosophila (Kloss et al 1998). 

Kloss B, Price JL, Saez L et al 1998 The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Is. Cell 94 97—107 Kloss B, Rothenfluh A, Young MW, Saez L 2001 Phosphorylation of period is influenced by cycling physical associations of double-time, period, and timeless In the Drosophila clock. Neuron 30 699-706... 

FIG. 5. Role of phosphorylation and degradation of clock protein PER in human normal fibroblasts. After the phosphorylation of hPERl by casein kinase, the ubiquitin-proteosome pathway may be involved in its degradation in human cells. 

Camacho F, Cilio M, Guo Y et al 2001 Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. FEES Lett 489 159-165 Delaunay F, Thisse C, Marchand O, Laudet V, Thisse B 2000 An inherited functional circadian clock in zebrafish embryos. Science 289 297-300 Dunlap J 1998 Circadian rhythms. An end in the beginning. Science 280 1548-1549 Ebisawa T, Uchiyama M, Kajimura N et al 2001 Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep 2 342-346 Edery I, Zwiebel LJ, Dembinska ME, Rosbash M 1994 Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci USA 91 2260-2264 Ishida N, Kaneko M, AUada R 1999 Biological clocks. Proc Natl Acad Sci USA 96 8819-8820... 

Kishimoto, A. Brown, M.S. Slaughter, C.A. Goldstein, J.L. Phosphorylation of serine 833 in cytoplasmic domain of low density lipoprotein receptor by a high molecular weight enzyme resembling casein kinase II. J. Biol. Chem., 262, 1344-1351 (1987)... 

Grosclaude, F., Mahe, M.-F. and Voglino, G. F. 1974B. The variant 0-E and the code for the phosphorylation of bovine caseins. FEBS Lett. 45, 3-5 (French). 

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