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

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posted on 2003-09-15, 00:00 authored by Victoria Foletta, M A Lim, J Soosairaiah, A P Kelly, E G Stanley, M Shannon, W He, S Das, J Massagué, O Bernard
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.

History

Journal

Journal of cell biology

Volume

162

Issue

6

Pagination

1089 - 1098

Publisher

Rockefeller University Press

Location

Birmingham, Ala.

ISSN

0021-9525

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2003, The Rockefeller University Press

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