التفاصيل البيبلوغرافية
| العنوان: |
BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. |
| المؤلفون: |
de Jesus Perez, Vinicio A.1, Ali, Ziad1, Alastalo, Tero-Pekka2, Ikeno, Fumiaki1, Sawada, Hirofumi2, Ying-Ju Lai2, Kleisli, Thomas2, Spiekerkoetter, Edda1, Xiumei Qu1, Rubinos, Laura H.3, Ashley, Euan1, Amieva, Manuel2, Dedhar, Shoukat4, Rabinovitch, Marlene2 marlener@stanford.edu |
| المصدر: |
Journal of Cell Biology. 1/10/2011, Vol. 192 Issue 1, p171-188. 18p. |
| مصطلحات موضوعية: |
*BONE morphogenetic proteins, *SMOOTH muscle, *CELL growth, *CELL motility, *MUSCLE cells |
| مستخلص: |
We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)--β-catenin (βC) and Wnt--planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt--dependent manner, induces βC transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via α4-integrins. ILK-1 then induces the Wnt--PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1--mediated motility. Transfection of a Dvl mutant that binds βC without activating RhoA-Rac1 not only prevents BMP-2--mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent .C activity. Interfering with the Dvl-dependent Wnt--PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2--mediated tandem activation of Wnt--βC and Wnt--PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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