Serine/threonine/tyrosine phosphorylation

Kosako, H Gotoh, Y Matsuda, S Ishikawa, M and Nishida, E. (1992). Xenopus MAP kinase activator is a serine/threonine/tyrosine kinase activated by threonine phosphorylation. EMBO J. 11 2903-2908. 

It has been shown that phosphorylation changes the local conformation of a protein and thereby affects the activity of the complete protein. 341 Phosphorylation of serine and threonine side chains often occurs (Scheme 2). Phosphoamino acids are readily characterized using 3H and 31P NMR experiments. The H and 31P NMR parameters are distinct for phosphorylated serine, threonine, and tyrosine and have also been used to identify both cis-and trans-O-phospho-4-hydroxy-L-proline. 35 Phosphorylation of Cys is rare, but it can be identified by NMR even in large proteins. 36 ... 

The CBS prediction server also provides services for predicting O-glycosylation sites (NetGly) in mammalian proteins (http //www.cbs.dtu.dk/services/NetQGly-2.0/) and phosphorylation sites (NetPhos) in eukaryotic proteins (http //www.cbs.dtu.dk/ services/NetPhos/). Paste the query sequence and click the Submit Sequence button to receive the predicted results. NetOGly returns tables of potential versus threshold assignments for threonine and serine residues as well as a plot of O-glycosylation potential versus sequence position. NetPhos returns tables of context (nanopeptides, [S,T,Y] + 4 residues) and scores for serine/threonine/tyrosine predictions. 

Other oncogenes were soon discovered in a variety of animal viruses, and as the techniques of DNA sequencing became more routine, a surprising number of these oncogenes were matched up with normal genes in animals and even in humans. But what was the role of these proto-oncogenes Most of them have now been shown to code for enzymes that help control the growth and differentiation of cells. In many instances, the enzymes are kinases that phosphorylate serine, threonine or tyrosine residues of other... 

One of the most widespread modifications is phosphorylation or dephosphorylation of various amino acid side chains (e.g., serine, threonine, tyrosine, and histidine). These kinds of modification are most often a part of complex regulatory pathways, frequently under hormonal control. (See kinase cascade). 

Proschel, C. Blouin, M.J. Gutowski, N.J. Ludwig, R. Noble, M. Limkl is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene, 11, 1271-1281 (1995)... 

Protein kinases, most of which phosphorylate tyrosine residues but a few phosphorylate serine/threonine residues... 

Tyrosine phosphorylated IRS interacts with and activates PI 3-kinase [3]. Binding takes place via the SRC homology 2 (SH2) domain of the PI 3-kinase regulatory subunit. The resulting complex consisting of INSR, IRS, and PI 3-kinase facilitates interaction of the activated PI 3-kinase catalytic subunit with the phospholipid substrates in the plasma membrane. Generation of PI 3-phosphates in the plasma membrane reemits phospholipid dependent kinases (PDKl and PDK2) which subsequently phosphorylate and activate the serine/threonine kinase Akt (synonym protein... 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

Enzyme that catalyses the transfer of the y-phosphoryl group of ATP to acceptor hydroxyl groups of serine, threonine and tyrosine residues in the protein. 

After their synthesis (translation), most proteins go through a maturation process, called post-translational modification that affects their activity. One common post-translational modification of proteins is phosphorylation. Two functional classes of enzymes mediate this reversible process protein kinases add phosphate groups to hydroxyl groups of serine, threonine and tyrosine in their substrate, while protein phosphatases remove phosphate groups. The phosphate-linking... 

This intermediate MAPK activator (MAPK kinase, MAPKK) is a 45 kDa phosphoprotein capable of phosphorylating MAPK on serine/threonine and tyrosine residues (Matsuda et al., 1992 Nakielny et al., 1992a Kosako et al., 1993). Like MAPK, the activity of MAPKK is regulated by phosphorylation. During oocyte maturation MAPKK is phosphorylated on threonine residues (Kosako et al., 1992), and this phosphorylation is required for its activity (Ahn et al., 1991 Gomez and Cohen, 1991 Kosako et al., 1992 Matsuda et al., 1992). MPF can activate both MAPKK and MAPK in vitro, with the activation of MAPK lagging behind that of MAPKK however, MPF cannot activate either purified MAPKK or MAPK that has been dephosphorylated by phosphatases (Matsuda et al., 1992). MAPKK and MAPK are therefore believed to function downstream of MPF (Fig. 3). 

Ben-David, Y., Letwin, K., Tannock, L., Bernstein, A., and Pawson, T. (1991). A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators. EMBO J. 10 317-325. 

Crews, C. M., Alessandrini, A. A., and Erikson, R. L. (1991). Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proc. Natl. Acad. Sci. USA 88 8845-8849. 

Morrison, D, K., Kaplan, D. R Escobedo, J. A., Rapp, U Roberts, T. M., and Williams, L. T. (1989). Direct activation of the serine/threonine kinase activity of Raf-1 through tyrosine phosphorylation by the PDGFP-receptor. Cell 58 649-657. 

Rossomando, A. J., Saanghcra, J. S., Marsden, L. A., Weber, M. J., Pelech, S. L., and Sturgill, T. W. (1991). Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylation. J. Biol. Chem. 266 20270-20275. 

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