Regulation Mechanisms for Activin Signaling

点击翻译按钮获取中文摘要

In this study, we attempted to elucidate molecular mechanisms for activin signal transduction which is regulated either intracellularly or extracellularly by novel protein factors, ARIP (Activin receptor interacting protein) and FLRG (Follistatin lile related gene).(1) ARIP2 has one PDZ domain in the NH_2-terminal region and one leucine-zipper-like domain in the COOH-terminal region. ARIP2 interacts specifically with activin type II receptors (ActRII) among the receptors for the TGF-β family by the PDZ domain. The COOH-terminal region of ARIP2 interacts with RalBP1. Interestingly, ARIP2 regulates endocytosis of ActRII through the Ral/RalBP1-dependent pathway.(2) We identified the rasGAP-binding protein (Dok-1) as one of essential proteins responsible for activin-induced apoptosis in mouse B cell. Dok- 1 acts as an adaptor protein linking receptor serine/threonine kinases with the Smads in activin signaling.(3) ALK7 is an orphan receptor serine/threonine kinase expressed in neuronal tissues as well as in pancreatic islets and pituitary gland. The receptor combination of ActRII and ALK7 is activated more preferentially by activins B and AB rather than Activin A. Activin B responsiveness is largely ALK7-dependent both in neuronal cells and pancreatic β cells.(4) We identified a mouse follistatin-like protein, FLRG, which has binding activity for the members of TGF-β family such as activin, BMP, myostatin (GDF8) and GDF11. The binding of FLRG to growth factors results in inhibition of their physiolosical functions.