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Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1

Foletta, Victoria C and Lim, Mei Ann and Soosairajah, Juliana and Kelly, April P and Stanley, Edouard G and Shannon, Mark and He, Wei and Das, Supratik and Massagué, Joan and Bernard, Ora (2003) Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. Journal of Cell Biology, 162 (6). pp. 1089-1098. ISSN 0021-9525 (print) 1540-8140 (online)

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Abstract

Bone morphogenetic proteins (BMPs) regulate multiple cellular processes, including cell differentiation and migration. Their signals are transduced by the kinase receptors BMPR-I and BMPR-II, leading to Smad transcription factor activation via BMPR-I. LIM kinase (LIMK) 1 is a key regulator of actin dynamics as it phosphorylates and inactivates cofilin, an actin depolymerizing factor. During a search for LIMK1-interacting proteins, we isolated clones encompassing the tail region of BMPR-II. Although the BMPR-II tail is not involved in BMP signaling via Smad proteins, mutations truncating this domain are present in patients with primary pulmonary hypertension (PPH). Further analysis revealed that the interaction between LIMK1 and BMPR-II inhibited LIMK1's ability to phosphorylate cofilin, which could then be alleviated by addition of BMP4. A BMPR-II mutant containing the smallest COOH-terminal truncation described in PPH failed to bind or inhibit LIMK1. This study identifies the first function of the BMPR-II tail domain and suggests that the deregulation of actin dynamics may contribute to the etiology of PPH.

Item Type: Article
Uncontrolled Keywords: LIM kinase 1, BMPR-II, cytoskeleton, F-actin, cofilin
Subjects: FOR Classification > 0304 Medicinal and Bimolecular Chemistry
Faculty/School/Research Centre/Department > College of Health and Biomedicine
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Depositing User: VUIR
Date Deposited: 04 Dec 2013 00:01
Last Modified: 06 Dec 2013 01:26
URI: http://vuir.vu.edu.au/id/eprint/22429
DOI: 10.1083/jcb.200212060
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Citations in Scopus: 181 - View on Scopus

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