التفاصيل البيبلوغرافية
| العنوان: |
c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16INK4a expression. |
| المؤلفون: |
Kua, Hui-Yi, Liu, Huijuan, Leong, Wai Fook, Li, Lili, Jia, Deyong, Ma, Gang, Hu, Yuanyu, Wang, Xueying, Chau, Jenny F. L., Chen, Ye-Guang, Mishina, Yuji, Boast, Sharon, Yeh, James, Xia, Li, Chen, Guo-Qiang, He, Lin, Goff, Stephen P., Li, Baojie |
| المصدر: |
Nature Cell Biology; Jul2012, Vol. 14 Issue 7, p727-737, 11p, 1 Color Photograph, 14 Graphs |
| مصطلحات موضوعية: |
OSTEOBLASTS, STEM cells, PROGENITOR cells, OSTEOPOROSIS genetics, PHOSPHORYLATION, BONE growth, PROTEIN-tyrosine kinase regulation |
| مستخلص: |
Defects in stem cell renewal or progenitor cell expansion underlie ageing-related diseases such as osteoporosis. Yet much remains unclear about the mechanisms regulating progenitor expansion. Here we show that the tyrosine kinase c-Abl plays an important role in osteoprogenitor expansion. c-Abl interacts with and phosphorylates BMPRIA and the phosphorylation differentially influences the interaction of BMPRIA with BMPRII and the Tab1-Tak1 complex, leading to uneven activation of Smad1/5/8 and Erk1/2, the canonical and non-canonical BMP pathways that direct the expression of p16INK4a. c-Abl deficiency shunts BMP signalling from Smad1/5/8 to Erk1/2, leading to p16INK4a upregulation and osteoblast senescence. Mouse genetic studies revealed that p16INK4a controls mesenchymal stem cell maintenance and osteoblast expansion and mediates the effects of c-Abl deficiency on osteoblast expansion and bone formation. These findings identify c-Abl as a regulator of BMP signalling pathways and uncover a role for c-Abl in p16INK4a expression and osteoprogenitor expansion. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
