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

Summary, in English

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 rnorphogenetic 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.

• Author: Sylke Hassel; M Yakymovych; U Hellman; Lars Rönnstrand; P Knaus; S Souchelnytskyi
• Department/s: Department of Translational Medicine
• Publishing year: 2006
• Language: English
• Pages: 457-467
• Publication/Series: Journal of Cellular Physiology
• Volume: 206
• Issue: 2
• Links: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16155937opt=Abstract; http://dx.doi.org/10.1002/jcp.20480
• Document type: Journal article
• Publisher: John Wiley & Sons Inc.
• Topic: Medicinal Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 1097-4652