| First Author | Schwappacher R | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 11 | Pages | 1537-50 |
| PubMed ID | 19424179 | Mgi Jnum | J:200390 |
| Mgi Id | MGI:5508584 | Doi | 10.1038/emboj.2009.103 |
| Citation | Schwappacher R, et al. (2009) Novel crosstalk to BMP signalling: cGMP-dependent kinase I modulates BMP receptor and Smad activity. EMBO J 28(11):1537-50 |
| abstractText | 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. |
