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 |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work