Pathway crosstalk between Ras/Raf and PI3K in promotion of M-CSF-induced MEK/ERK-mediated osteoclast survival.
Pathway crosstalk between Ras/Raf and PI3K in promotion of M-CSF-induced MEK/ERK-mediated osteoclast survival.
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DOI：
10.1002/jcb.21719
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发表时间：
2008-07-01
影响因子：
4
通讯作者：
Oursler, Merry Jo
中科院分区：
文献类型：
--
作者：
Bradley, Elizabeth W.;Ruan, Ming M.;Vrable, Anne;Oursler, Merry Jo
While M-CSF-mediated MEK/ERK activation promotes osteoclast survival, the signaling pathway by which M-CSF activates MEK/ERK is unresolved. Functions for PI3K, Ras, and Raf have been implicated in support of osteoclast survival, although interaction between these signaling components has not been examined. Therefore, the interplay between PI3K, Ras and Raf in M-CSF-promoted MEK/ERK activation and osteoclast survival was investigated. M-CSF activates Ras to coordinate activation of PI3K and Raf/MEK/ERK, since Ras inhibition decreased PI3K activation and PI3K inhibition did not block M-CSF-mediated Ras activation. As further support for Ras-mediated signaling, constitutively active (ca) Ras promoted MEK/ERK activation and osteoclast survival, which was blocked by inhibition of PI3K or Raf. Moreover, PI3K-selective or Raf-selective caRas were only partially able to promote osteoclast survival when compared to parental caRas. We then examined whether PI3K and Raf function linearly or in parallel downstream of Ras. Expression of caPI3K increased MEK/ERK activation and promoted osteoclast survival downstream of M-CSF, supporting this hypothesis. Blocking Raf did not decrease osteoclast survival and MEK/ERK activation promoted by caPI3K. In addition, PI3K-selective Ras-mediated survival was not blocked by Raf inhibition. Taken together, our data support that Raf signaling is separate from Ras/PI3K signaling and PI3K signaling is separate from Ras/Raf signaling. These data therefore support a role for Ras in coordinate activation of PI3K and Raf acting in parallel to mediate MEK/ERK-promoted osteoclast survival induced by M-CSF.
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DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
通讯作者：
Suda T
影响因子：
6.2
作者：
Luckman, SP;Hughes, DE;Rogers, MJ
通讯作者：
Rogers, MJ
影响因子：
4.1
作者：
Jaworowski, A;Christy, E;Hamilton, JA
通讯作者：
Hamilton, JA
影响因子：
4.8
作者：
Sato, S;Fujita, N;Tsuruo, T
通讯作者：
Tsuruo, T
巨噬细胞刺激因子刺激分离的破骨细胞中的存活和趋化行为。
DOI：
10.1084/jem.178.5.1733
发表时间：
1993-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuller K;Owens JM;Jagger CJ;Wilson A;Moss R;Chambers TJ
通讯作者：
Chambers TJ