Interaction and functional cooperation between the serine/threonine kinase bone morphogenetic protein type II receptor with the tyrosine kinase stem cell factor receptor

J Cell Physiol. 2006 Feb;206(2):457-67. doi: 10.1002/jcp.20480.


Transmembrane receptors with intrinsic serine/threonine or tyrosine kinase domains regulate vital functions of cells in multicellular eukaryotes, e.g., differentiation, apoptosis, and proliferation. Here, we show that bone morphogenetic protein type II receptor (BMPR-II) which has a serine/threonine kinase domain, and stem cell factor receptor (c-kit) which contains a tyrosine kinase domain form a complex in vitro and in vivo; the interaction is induced upon treatment of cells with BMP2 and SCF. Stem cell factor (SCF) modulated BMP2-dependent activation of Smad1/5/8 and phosphorylation of Erk kinase. SCF also enhanced BMP2-dependent differentiation of C2C12 cells. We found that BMPR-II was phosphorylated at Ser757 upon co-expression with and activation of c-kit. BMPR-II phosphorylation required intact kinase activity of BMPR-II. Abrogation of the c-kit/SCF-dependent phosphorylation of BMPR-II at the Ser757 interfered with the cooperative effect of BMP2 and SCF. Our data suggest that the complex formation between c-kit and BMPR-II leads to phosphorylation of BMPR-II at Ser757, which modulates BMPR-II-dependent signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type II / chemistry
  • Bone Morphogenetic Protein Receptors, Type II / metabolism
  • Bone Morphogenetic Protein Receptors, Type II / physiology*
  • COS Cells
  • Cell Differentiation
  • Cells, Cultured
  • Chlorocebus aethiops
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Mice
  • Mutation
  • Phosphorylation
  • Proto-Oncogene Proteins c-kit / chemistry
  • Proto-Oncogene Proteins c-kit / metabolism
  • Proto-Oncogene Proteins c-kit / physiology*
  • Receptor Cross-Talk*
  • Signal Transduction
  • Smad Proteins / metabolism
  • Transfection


  • Smad Proteins
  • Proto-Oncogene Proteins c-kit
  • Extracellular Signal-Regulated MAP Kinases
  • Bone Morphogenetic Protein Receptors, Type II