RRC ID 43757
著者 Sugiyama G, Takeuchi H, Nagano K, Gao J, Ohyama Y, Mori Y, Hirata M.
タイトル Regulated interaction of protein phosphatase 1 and protein phosphatase 2A with phospholipase C-related but catalytically inactive protein.
ジャーナル Biochemistry
Abstract Protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) are major members of the protein serine/threonine phosphatase families. We have identified PP1 and PP2A as interacting partners of PRIP (phospholipase C-related but catalytically inactive protein), a protein isolated in our laboratory. We first investigated the interaction of PRIP with two phosphatases, using purified recombinant proteins. PRIP immobilized on beads pulled down the catalytic subunits of both PP1 and PP2A, indicating that the interactions were in a direct manner, and the binding of PP1 and the binding of PP2A to PRIP were mutually exclusive. Site-directed mutagenesis experiments revealed that the binding sites for PP1 and PP2A on PRIP were not identical, but similar. Phosphorylation of PRIP by protein kinase A (PKA) resulted in the weakened binding of PP1, but not PP2A. Rather, the dissociation of PP1 from PRIP by phosphorylation accompanied the strengthened binding of PP2A in in vitro experiments. This regulation of binding of PP1 and PP2A to PRIP by PKA-dependent phosphorylation was also observed in living cells treated with forskolin or isoproterenol. These results suggested that PRIP directly interacts with the catalytic subunits of two distinct phosphatases in a mutually exclusive manner and the interactions are regulated by phosphorylation, thus functioning as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling.
巻・号 51(16)
ページ 3394-403
公開日 2012-4-24
DOI 10.1021/bi2018128
PMID 22458807
MeSH Animals Binding Sites COS Cells Catalytic Domain Chlorocebus aethiops Mutagenesis, Site-Directed Phosphorylation Protein Phosphatase 1 / chemistry Protein Phosphatase 1 / genetics Protein Phosphatase 1 / metabolism* Protein Phosphatase 2 / chemistry Protein Phosphatase 2 / genetics Protein Phosphatase 2 / metabolism* Signal Transduction Transfection
IF 2.865
引用数 10
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞