Interaction and functional cooperation between the serine/threonine kinase bone morphogenetic protein type II receptor with the tyrosine kinase stem cell factor receptor
✍ Scribed by Sylke Hassel; Mariya Yakymovych; Ulf Hellman; Lars Rönnstrand; Petra Knaus; Serhiy Souchelnytskyi
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 450 KB
- Volume
- 206
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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. J. Cell. Physiol. 206: 457–467, 2006. © 2005 Wiley‐Liss, Inc.