Abstract
Background: BMP2 is known to play a wide variety of roles, including some in the development of the nervous system. This cytokine has been reported to induce neurite outgrowth in rat pheochromocytoma PC12 cells via the activation of a p38 MAP kinase, although its regulatory mechanism remains largely to be elucidated. Results: BMP2-induced neurite outgrowth in PC12 cells was inhibited by the introduction of a kinase-negative form of a MAP kinase kinase kinase, TAK1, an upstream regulatory kinase for p38 kinase. Following BMP2 stimulation, the expression of Smad6 and Smad7, inhibitory Smad species that are known to inhibit the BMP2-restricted Smad species, Smad1, Smad5 and Smad8, was up-regulated. Unexpectedly, over-expression of either Smad6 or Smad7 in PC12 cells repressed the BMP2-induced neurite outgrowth and severely impeded the p38 kinase pathway. Both of these inhibitory Smads were found to interact physically with TAK1-binding protein, a molecule required for TAK1 activation. Conclusions: This study demonstrates that BMP2-induced neurite outgrowth in PC12 cells involves activation of the TAK1-p38 kinase pathway which is inhibited by Smad6 and Smad7.
| Original language | English |
|---|---|
| Pages (from-to) | 1091-1099 |
| Number of pages | 9 |
| Journal | Genes to Cells |
| Volume | 6 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 24 2001 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Genetics
- Cell Biology
Cite this
Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7. / Yanagisawa, Makoto; Nakashima, Kinichi; Takeda, Kohsuke; Ochiai, Wataru; Takizawa, Takumi; Ueno, Masaya; Takizawa, Makiko; Shibuya, Hiroshi; Taga, Tetsuya.
In: Genes to Cells, Vol. 6, No. 12, 24.12.2001, p. 1091-1099.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7
AU - Yanagisawa, Makoto
AU - Nakashima, Kinichi
AU - Takeda, Kohsuke
AU - Ochiai, Wataru
AU - Takizawa, Takumi
AU - Ueno, Masaya
AU - Takizawa, Makiko
AU - Shibuya, Hiroshi
AU - Taga, Tetsuya
PY - 2001/12/24
Y1 - 2001/12/24
N2 - Background: BMP2 is known to play a wide variety of roles, including some in the development of the nervous system. This cytokine has been reported to induce neurite outgrowth in rat pheochromocytoma PC12 cells via the activation of a p38 MAP kinase, although its regulatory mechanism remains largely to be elucidated. Results: BMP2-induced neurite outgrowth in PC12 cells was inhibited by the introduction of a kinase-negative form of a MAP kinase kinase kinase, TAK1, an upstream regulatory kinase for p38 kinase. Following BMP2 stimulation, the expression of Smad6 and Smad7, inhibitory Smad species that are known to inhibit the BMP2-restricted Smad species, Smad1, Smad5 and Smad8, was up-regulated. Unexpectedly, over-expression of either Smad6 or Smad7 in PC12 cells repressed the BMP2-induced neurite outgrowth and severely impeded the p38 kinase pathway. Both of these inhibitory Smads were found to interact physically with TAK1-binding protein, a molecule required for TAK1 activation. Conclusions: This study demonstrates that BMP2-induced neurite outgrowth in PC12 cells involves activation of the TAK1-p38 kinase pathway which is inhibited by Smad6 and Smad7.
AB - Background: BMP2 is known to play a wide variety of roles, including some in the development of the nervous system. This cytokine has been reported to induce neurite outgrowth in rat pheochromocytoma PC12 cells via the activation of a p38 MAP kinase, although its regulatory mechanism remains largely to be elucidated. Results: BMP2-induced neurite outgrowth in PC12 cells was inhibited by the introduction of a kinase-negative form of a MAP kinase kinase kinase, TAK1, an upstream regulatory kinase for p38 kinase. Following BMP2 stimulation, the expression of Smad6 and Smad7, inhibitory Smad species that are known to inhibit the BMP2-restricted Smad species, Smad1, Smad5 and Smad8, was up-regulated. Unexpectedly, over-expression of either Smad6 or Smad7 in PC12 cells repressed the BMP2-induced neurite outgrowth and severely impeded the p38 kinase pathway. Both of these inhibitory Smads were found to interact physically with TAK1-binding protein, a molecule required for TAK1 activation. Conclusions: This study demonstrates that BMP2-induced neurite outgrowth in PC12 cells involves activation of the TAK1-p38 kinase pathway which is inhibited by Smad6 and Smad7.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035207033&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2443.2001.00483.x
DO - 10.1046/j.1365-2443.2001.00483.x
M3 - Article
VL - 6
SP - 1091
EP - 1099
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 12
ER -