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

Foletta, VC; Lim, MA; Soosairaiah, J; Kelly, AP; Stanley, EG; Shannon, M; He, W; Das, S; Massague, J; Bernard, O

Author(s): Foletta, VC; Lim, MA; Soosairaiah, J; Kelly, AP; Stanley, EG; Shannon, M; He, W; Das, S; Massague, J; Bernard, O;
Details: Publication Year 2003-09-15,Volume 162,Issue #6,Page 1089-1098
Journal Title: JOURNAL OF CELL BIOLOGY
Publication Type: Journal Article
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 IMPR-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.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: PRIMARY PULMONARY-HYPERTENSION; TGF-BETA RECEPTOR; ACTIN POLYMERIZATION; GERMLINE MUTATIONS; ZINC-FINGER; PROTEIN; KINASE; COFILIN; GROWTH; PHOSPHORYLATION
Publisher's Version: https://doi.org/10.1083/jcb.200212060
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2003-09-15 12:00:00