Novel crosstalk to BMP signalling: CGMP-dependent kinase i modulates BMP receptor and Smad activity

Raphaela Schwappacher, Jörg Weiske, Eva Heining, Verena Ezerski, Barak Marom, Yoav I. Henis, Otmar Huber, Petra Knaus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Integration of multiple signals into the canonical BMP/Smad pathway poses a big challenge during the course of embryogenesis and tissue homeostasis. Here, we show that cyclic guanosine 3′,5′-monophosphate (cGMP)-dependent kinase I (cGKI) modulates BMP receptors and Smads, providing a novel mechanism enhancing BMP signalling. cGKI, a key mediator of vasodilation and hypertension diseases, interacts with and phosphorylates the BMP type II receptor (BMPRII). In response to BMP-2, cGKI then dissociates from the receptors, associates with activated Smads, and undergoes nuclear translocation. In the nucleus, cGKI binds with Smad1 and the general transcription factor TFII-I to promoters of BMP target genes such as Id1 to enhance transcriptional activation. Accordingly, cGKI has a dual function in BMP signalling: (1) it modulates BMP receptor/Smad activity at the plasma membrane and (2) after redistribution to the nucleus, it further regulates transcription as a nuclear co-factor for Smads. Consequently, cellular defects caused by mutations in BMPRII, found in pulmonary arterial hypertension patients, were compensated through cGKI, supporting the positive action of cGKI on BMP-induced Smad signalling downstream of the receptors.

Original languageEnglish
Pages (from-to)1537-1550
Number of pages14
JournalEMBO Journal
Issue number11
StatePublished - 3 Jun 2009


  • Bone morphogenetic protein
  • CGMP-dependent protein kinase
  • Pulmonary arterial hypertension
  • Smad
  • TFII-I


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