Title: Protein phosphatase-1 is a novel regulator of the interaction between IRBIT and the inositol 1,4,5-trisphosphate receptor
Authors: Devogelaere, Benoit ×
Beullens, Monique
Sammels, Eva
Derua, Rita
Waelkens, Etienne
Van Lint, Johan
Parys, Jan
Missiaen, Ludwig
Bollen, Mathieu
De Smedt, Humbert #
Issue Date: Oct-2007
Publisher: Published by Portland Press on behalf of the Biochemical Society
Series Title: Biochemical Journal vol:407 issue:2 pages:303-311
Abstract: IRBIT is an IP3R [IP3 (inositol 1,4,5-trisphosphate) receptor]-binding protein that competes with IP3 for binding to the IP3R. Phosphorylation of IRBIT is essential for the interaction with the IP3R. The unique N-terminal region of IRBIT, residues 1-104 for mouse IRBIT, contains a PEST (Pro-Glu-Ser-Thr) domain with many putative phosphorylation sites. In the present study, we have identified a well-conserved PP1 (protein phosphatase-1)-binding site preceeding this PEST domain which enabled the binding of PP1 to IRBIT both in vitro and in vivo. IRBIT emerged as a mediator of its own dephosphorylation by associated PP1 and, hence, as a novel substrate specifier for PP1. Moreover, IRBIT-associated PP1 specifically dephosphorylated Ser68 of IRBIT. Phosphorylation of Ser68 was required for subsequent phosphorylation of Ser71 and Ser74, but the latter two sites were not targeted by PP1. We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R by IRBIT. Finally, we have shown that mutational inactivation of the docking site for PP1 on IRBIT increased the affinity of IRBIT for the IP3R. This pinpoints PP1 as a key player in the regulation of IP3R-controlled Ca2+ signals.
ISSN: 0264-6021
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Biochemistry Section (Medicine) (-)
Laboratory of Biosignaling & Therapeutics
Laboratory of Phosphoproteomics (-)
Laboratory of Protein Phosphorylation and Proteomics
Laboratory of Molecular and Cellular Signaling
× corresponding author
# (joint) last author

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