Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.
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 NH2-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.
Liu
Z H
ZH
The Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Tsuchida
K
K
Matsuzaki
T
T
Bao
Y L
YL
Kurisaki
A
A
Sugino
H
H
D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D004705:Endocytosis / Q000502:physiology; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007536:Isomerism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C492525:Reps2 protein, mouse; C457224:Synj2bp protein, mouse; D028341:Activins; D005640:Follicle Stimulating Hormone; D030301:Activin Receptors, Type II