Regulation of neurabin I interaction with protein phosphatase 1 by phosphorylation.
Neurabin I is a brain-specific actin-binding protein. Here we show that neurabin I binds protein phosphatase 1 ( PP1) and inhibits PP1 activity. Neurabin I interacted with PP1alpha in an overlay assay, in yeast two-hybrid interaction analysis, and in coprecipitation and co-immunoprecipitation experiments. Neurabin I also copurified with both the alpha and gamma isoforms of PP1. A glutathione S-transferase (GST)-neurabin I fusion protein (residues 318-661) containing the putative PP1 binding domain (residues 456-460) inhibited PP1 activity (K(i) = 2.7 +/- 1.2 nM). This fusion protein was also rapidly phosphorylated in vitro by PKA (K(m) = 6 microM) to a stoichiomtry of 1 mol/mol. The phosphorylated residue was identified as serine 461 by HPLC-MS analysis of a tryptic digest. Phosphorylation of GST- neurabin I (residues 318-661) by PKA significantly reduced its binding to PP1 by overlay and by glutathione-Sepharose coprecipitation assays. A 35-fold decrease in inhibitory potency was also observed using a S461E mutant, which mimics phosphorylation of S461. These findings identify a signaling mechanism involving the regulation of PP1 activity and localization mediated by the cAMP pathway.[1]References
- Regulation of neurabin I interaction with protein phosphatase 1 by phosphorylation. McAvoy, T., Allen, P.B., Obaishi, H., Nakanishi, H., Takai, Y., Greengard, P., Nairn, A.C., Hemmings, H.C. Biochemistry (1999) [Pubmed]
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