Protein phosphatase-1 interacting proteins

S100A4, like some other S100 proteins, is able to relocate upon cellular stimulation, allowing its interaction with different partner proteins in a spatial and temporal manner. These include liprin (31, a member of the family of LAR transmembrane phosphatase -interacting proteins (Kriajevska et al., 2002), annexin II (Semov et al., 2005), p53 (Grigorian et al., 2001), methionine aminopep-tidase 2 (Endo et al., 2002), or myosin-IIA heavy chain (Li and Bresnick, 2006). 

Serra-Pages C, Medley QG, Tang M, Hart A, Streuli M (1998) Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem 275 15611-15620. 

Numerous protein phosphatases are targeted to their substrates and regulators through the interaction with specific scaffolding proteins. Some of these anchoring proteins bind both, kinases and phosphatases. This applies to ser/thr protein phosphatases as well as to tyrosine phosphatases. 

Regulation of protein phosphorylation involves a protein kinase, a protein phosphatase and a substrate protein. These components interact according to the scheme shown in Figure 23-1. A substrate protein is converted from the dephospho form to the phospho form by a protein kinase, and the phospho form is converted back to the dephospho form by a protein phosphatase [1]. 

The cAMP and Ca2+ pathways also interact at the level of protein kinases and protein phosphatases. This is illustrated by inhibitor-1 and DARPP-32, which are phosphorylated and activated by PKA and then inhibit PP1, which can dephosphorylate numerous substrates for Ca2+-dependent protein kinases. Another example is the physical association between PKA and PP2B (a Ca2+/ calmodulin-activated enzyme) via the AKAP-anchoring proteins. 

Even more interesting is the observed regioselectivity of 37 its reaction with 2, 3 -cCMP and 2, 3 -cUMP resulted in formation of more than 90% of 2 -phosphate (3 -OH) isomer. The postulated mechanisms for 37 consists of a double Lewis-acid activation, while the metal-bound hydroxide and water act as nucleophilic catalyst and general acid, respectively (see 39). The substrate-ligand interaction probably favors only one of the depicted substrate orientations, which may be responsible for the observed regioselectivity. Complex 38 may operate in a similar way but with single Lewis-acid activation, which would explain the lower bimetallic cooperativity and the lack of regioselectivity. Both proposed mechanisms show similarities to that of the native phospho-monoesterases (37 protein phosphatase 1 and fructose 1,6-diphosphatase, 38 purple acid phosphatase). 

Das, a. K., P. W. Cohen, and D. Bareord, The structure of the tetratricopeptide repeats of protein phosphatase 5 implications for TPR-mediated protein-protein interactions. EmboJ, 1998, 17(5), 1192-9. 

The principle of targeted localization is shown in Fig. 7.22. In addition to the binding site for the corresponding protein kinase (or protein phosphatase), the localization subunit also has a specific binding site for an anchor protein, found at a subceUular site in the region where protein phosphorylation should take place. Through the interaction of anchor protein and localization subunit, the catalytic subunit is fixed at the desired location and is able to preferentially convert substrate localized at the same location. 

Fig. 7.22. The prindple of targeted localization of protein kinases and protein phosphatases. The spatial configuration between the catalytic subunit of a protein kinase or protein phosphatase and a membrane-associated substrate is mediated by localization subunits that specifically bind to membrane-localized anchor proteins. The specificity of co-localization is predominantly achieved at the level of binding of the localization subunit to the anchor protein. The co-localization is regulated, in particular, by the interaction of the catalytic subunit with the localization subunit. In the membrane-associated form, the catalytic subunit has increased activity towards membrane-bound substrates.

Hie subcdlular localization of the kinase or phosphatase also plays a crucial role for the activity of protein kinases and protein phosphatases. Many physiological functions of protein kinases and protein phosphatases depend on the enzyme being brought, with the help of specific protein-protein interactions, to certain subceUular locations in the vicinity of its substrate. 

Furthermore, the structure of microcystin includes an electrophilic carbon atom, (Fig. 7.26), which is part of the Mdha amino acid. If microcystin is ingested from contaminated water, for example, it is taken up into the liver by an organic anion transporter (OAT) system and therefore is concentrated in the liver. The structure of the microcystins means they are able to associate with the enzymes protein phosphatases, such as PP-1, PP-2A, and PP-2B via hydrophobic and ionic interactions. 

Protein phosphatases 544, 646 Protein S 634 Protein sequenators 118 Protein sequences from genes 119 Protein synthesis 3, 538, 539 Protein tyrosine kinases 544 Protein-disulfide isomerase 83 Protein-DNA interactions 266 Proteinase. See Protease Proteoglycan(s) 181,182. See also Glycosami-noglycans... 

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