These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins.
    Author: Kwon YG, Huang HB, Desdouits F, Girault JA, Greengard P, Nairn AC.
    Journal: Proc Natl Acad Sci U S A; 1997 Apr 15; 94(8):3536-41. PubMed ID: 9108011.
    Abstract:
    The catalytic subunit of PP-1 (PP-1C) is potently inhibited (IC50, approximately 1 nM) by DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) 32,000), inhibitor-1, and inhibitor-2. The NH2-terminal 50 amino acid residues of DARPP-32 and inhibitor-1 are similar, and phosphorylation of a common threonine residue (Thr-34/Thr-35) is necessary for inhibition of PP-1C. We have characterized further the interaction between DARPP-32 and PP-1C. Using synthetic peptides derived from the NH2-terminal region of DARPP-32, residues 6-11, RKKIQF, have been shown to be required for inhibition of PP-1C. Peptides containing this motif were able to antagonize the inhibition of PP-1C by phospho-DARPP-32 and phosphoinhibitor-1. The inhibition of PP-1C by inhibitor-2, but not by okadaic acid, microcystin, or calyculin A, was also attentuated by these antagonist peptides. These results together with results from other studies support a model in which two subdomains of phospho-DARPP-32 interact with PP-1C. The region encompassing phospho-Thr-34 appears to interact with the active site of the enzyme blocking enzyme activity. The region encompassing the RKKIQF motif binds to a domain of PP-1C removed from the active site. Amino acid sequence analysis indicates that basic and hydrophobic features of the RKKIQF motif are conserved in the binding domains of certain PP-1C targeting proteins, suggesting that interaction of inhibitor proteins and targeting proteins may be mutually exclusive.
    [Abstract] [Full Text] [Related] [New Search]