TAK1-binding protein 1 is a pseudophosphatase.
TAB1 [ TAK1 (transforming growth factor-beta-activated kinase 1)-binding protein 1] is one of the regulatory subunits of TAK1, a protein kinase that lies at the head of three pro-inflammatory kinase cascades. In the current study we report the crystal structure of the N-terminal domain of TAB1. Surprisingly, TAB1 possesses a fold closely related to that of the PPM (Mg(2+)- or Mn(2+)-dependent protein phosphatase) family as demonstrated by the close structural similarity with protein phosphatase 2Calpha. However, we were unable to detect any phosphatase activity for TAB1 using a phosphopeptide or p-nitrophenyl phosphate as substrate. Although the overall protein phosphatase 2Calpha fold is conserved in TAB1, detailed structural analyses and mutagenesis studies show that several key residues required for dual metal-binding and catalysis are not present in TAB1, although binding of a single metal is supported by soaking experiments with manganese and isothermal titration calorimetry. Thus, it appears that TAB1 is a 'pseudophosphatase', possibly binding to and regulating accessibility of phosphorylated residues on substrates downstream of TAK1 or on the TAK1 complex itself.[1]References
- TAK1-binding protein 1 is a pseudophosphatase. Conner, S.H., Kular, G., Peggie, M., Shepherd, S., Sch??ttelkopf, A.W., Cohen, P., Van Aalten, D.M. Biochem. J. (2006) [Pubmed]
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