Identification and characterization of a PDZ protein that interacts with activin type II receptors

Hiroki Shoji, Kunihiro Tsuchida, Hisashi Kishi, Norio Yamakawa, Takashi Matsuzaki, Zhong Hui Liu, Takanori Nakamura, Hiromu Sugino

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Abstract

We have identified a mouse PDZ protein that interacts with the activin type IIA receptor (ActRIIA), which we named activin receptor-interacting protein 1 (ARIP1). By using yeast two-hybrid screening, we isolated a cDNA clone of ARIP1 from a mouse brain cDNA library. We detected two forms of ARIP1, ARIP1-long and ARIP1-short, which may be produced by alternative splicing. ARIP1-long had one guanylate kinase domain in the NH2-terminal region, followed by two WW domains and five PDZ domains (PDZ1-5). ARIP1-short had a deletion in the NH2-terminal region and lacked the guanylate kinase domain. Both forms interacted with ActRIIA through PDZ5. The COOH-terminal residues of ActRIIA (ESSL) agree with a PDZ-binding consensus motif, and ARIP1 recognized the consensus sequence. ARIP1 interacts specifically with ActRIIA among the receptors for the transforming growth factor β family. Interestingly, ARIP1 also interacted with Smad3, which is an activin/transforming growth factor β intracellular signaling molecule. The mRNA of ARIP1 was more abundant in the brain than in other tissues. Overexpression of ARIP1 controls activin-induced and Smad3-induced transcription in activin-responsive cell lines. These findings suggest that ARIP1 has a significant role in assembling activin signaling molecules at specific subcellular sites and in regulating signal transduction in neuronal cells.

Original languageEnglish
Pages (from-to)5485-5492
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number8
DOIs
Publication statusPublished - 25-02-2000

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Shoji, H., Tsuchida, K., Kishi, H., Yamakawa, N., Matsuzaki, T., Liu, Z. H., Nakamura, T., & Sugino, H. (2000). Identification and characterization of a PDZ protein that interacts with activin type II receptors. Journal of Biological Chemistry, 275(8), 5485-5492. https://doi.org/10.1074/jbc.275.8.5485