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


Authors: Foletta, V. C.; Lim, M. A.; Soosairaiah, J.; Kelly, A. P.; Stanley, E. G.; Shannon, M.; He, W.; Das, S.; Massagué, J.; Bernard, O.
Article Title: Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1
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.
Keywords: signal transduction; controlled study; protein phosphorylation; unclassified drug; mutation; dna-binding proteins; nonhuman; biological markers; animal cell; animals; protein kinases; bone morphogenetic protein receptor; smad protein; protein protein interaction; cell protein; molecular dynamics; transcription factor; cell differentiation; cos cells; phosphorylation; animalia; protein-serine-threonine kinases; cell migration; smad proteins; protein structure, tertiary; trans-activators; up-regulation; cytoskeleton; pulmonary artery; bone morphogenetic proteins; pulmonary hypertension; bone morphogenetic protein 4; hypertension, pulmonary; cofilin; eukaryotic cells; bone morphogenetic protein receptor 1; actin depolymerizing factor; f-actin; humans; priority journal; article; bmpr-ii; lim kinase 1; bone morphogenetic protein receptor 2; protein limk1; bone morphogenetic protein receptors, type ii
Journal Title: Journal of Cell Biology
Volume: 162
Issue: 6
ISSN: 0021-9525
Publisher: Rockefeller University Press  
Date Published: 2003-09-15
Start Page: 1089
End Page: 1098
Language: English
DOI: 10.1083/jcb.200212060
PUBMED: 12963706
PROVIDER: scopus
PMCID: PMC2172847
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Supratik Das
    1 Das
  2. Wei He
    6 He
  3. Joan Massague
    389 Massague