• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 12963706

Authors

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

Journal

The Journal of cell biology

Publication Data

September 15, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: CA34610

Mesh Terms

  • Animals
  • Biological Markers
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein Receptors, Type II
  • Bone Morphogenetic Proteins
  • COS Cells
  • Cytoskeleton
  • DNA-Binding Proteins
  • Eukaryotic Cells
  • Humans
  • Hypertension, Pulmonary
  • Lim Kinases
  • Mutation
  • Phosphorylation
  • Protein Kinases
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Pulmonary Artery
  • Signal Transduction
  • Smad Proteins
  • Trans-Activators
  • Up-Regulation