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The Rho-associated serine/threonine kinases Rock1 and Rock2 play important roles in cell contraction, adhesion, migration, proliferation and apoptosis. Here we report that Rock2 acts as a negative regulator of the TGFβ signaling pathway. Mechanistically, Rock2 binds to and accelerates the lysosomal degradation of TGFβ type I receptors internalized from the cell surface in mammalian cells. The inhibitory effect of Rock2 on TGFβ signaling requires its kinase activity. In zebrafish embryos, injection of rock2a mRNA attenuates the expression of mesodermal markers during late blastulation and blocks the induction of mesoderm by ectopic Nodal signals. By contrast, overexpression of a dominant negative form of zebrafish rock2a, dnrock2a, has an opposite effect on mesoderm induction, suggesting that Rock2 proteins are endogenous inhibitors for mesoderm induction. Thus, our data have unraveled previously unidentified functions of Rock2, in controlling TGFβ signaling as well as in regulating embryonic patterning.


  • We are grateful to Zhenguo Wu and Min Li for suggestions and comments. We acknowledge members of Y. G. Chen's laboratory (Tsinghua University, Beijing, China) for technical assistance and reagents. We thank Lilianna Solnica-Krezel for providing zebrafish rock2 cDNA and Frederic Rosa (Ecole Normale Supérieure, Paris, France) for providing taram constructs. This work was supported by grants from the National Basic Research Program of China (#2005CB522502), the Major Science Programs of China (#2006CB943401) and the `863 Program' (#2006AA02Z167).

  • Accepted March 16, 2009.
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