- Title
- Multiple interactions within the AKAP220 signaling complex contribute to protein phosphatase 1 regulation
- Creator
- Schillace, Robynn V.; Voltz, James W.; Sim, Alistair T. R.; Shenolikar, Shirish; Scott, John D.
- Relation
- Journal of Biological Chemistry Vol. 276, Issue 15, p. 12128-12134
- Publisher Link
- http://dx.doi.org/10.1074/jbc.M010398200
- Publisher
- American Society for Biochemistry and Molecular Biology
- Resource Type
- journal article
- Date
- 2001
- Description
- The phosphorylaton status of cellular proteins is controlled by the opposing actions of protein kinases and phosphatases. Compartmentalization of these enzymes is critical for spatial and temporal control of these phosphorylation/dephosphorylation events. We previously reported that a 200 kDa A-Kinase Anchoring Protein, AKAP220, coordinates the location of the cAMP dependent protein kinase (PKA) and the type 1 protein phosphatase (PP1c) [Schillace, R. V., and Scott, J. D. (1999) Curr Biol 9, 321-4]. We now demonstrate that a fragment of AKAP220 is a competitive inhibitor of PP1c activity (Ki = 2.9 ± 0.7 µM n=3). Mapping studies and activity measurements indicate that several protein-protein interactions act synergistically to inhibit PP1. A consensus targeting motif, between residues 1195 to 1198 (Lys-Val-Gln-Phe) binds but does not effect enzyme activity whereas determinants between residues 1711-1901 inhibit the phosphatase. Analysis of truncated PP1c and chimeric PP1/2A catalytic subunits suggest that AKAP220 inhibits the phosphatase in a manner distinct from all known PP1 inhibitors and toxins. Intermolecular interactions within the AKAP220 signaling complex further contribute to PP1 inhibition as addition of the PKA regulatory subunit (RII) enhances phosphatase inhibition. These experiments indicate that regulation of PP1 activity by AKAP220 involves a complex network of intra- and inter-molecular interactions.
- Subject
- phosphorylaton status; cellular proteins; protein kinases; protein phosphatases
- Identifier
- http://hdl.handle.net/1959.13/27744
- Identifier
- uon:1966
- Identifier
- ISSN:0021-9258
- Language
- eng
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