Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling

Z. H. Liu, Kunihiro Tsuchida, T. Matsuzaki, Y. L. Bao, A. Kurisaki, H. Sugino

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif ARIP2 and its isoforms have one PDZ domain in the NH 2 -terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/ 2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.

Original languageEnglish
Pages (from-to)409-421
Number of pages13
JournalJournal of Endocrinology
Volume189
Issue number2
DOIs
Publication statusPublished - 01-05-2006

Fingerprint

Activin Receptors
Receptor-Interacting Protein Serine-Threonine Kinases
PDZ Domains
Activins
Protein Isoforms
Protein-Serine-Threonine Kinases
Type II Activin Receptors
Myostatin
Bone Morphogenetic Proteins
Proteins
Kidney
Liver
Brain

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Liu, Z. H. ; Tsuchida, Kunihiro ; Matsuzaki, T. ; Bao, Y. L. ; Kurisaki, A. ; Sugino, H. / Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling. In: Journal of Endocrinology. 2006 ; Vol. 189, No. 2. pp. 409-421.
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abstract = "Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif ARIP2 and its isoforms have one PDZ domain in the NH 2 -terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/ 2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.",
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Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling. / Liu, Z. H.; Tsuchida, Kunihiro; Matsuzaki, T.; Bao, Y. L.; Kurisaki, A.; Sugino, H.

In: Journal of Endocrinology, Vol. 189, No. 2, 01.05.2006, p. 409-421.

Research output: Contribution to journalArticle

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