Rock2 controls TGFbeta signaling and inhibits mesoderm induction in zebrafish embryos.
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 TGFbeta signaling pathway. Mechanistically, Rock2 binds to and accelerates the lysosomal degradation of TGFbeta type I receptors internalized from the cell surface in mammalian cells. The inhibitory effect of Rock2 on TGFbeta 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 TGFbeta signaling as well as in regulating embryonic patterning.
Zhang
Yu
Y
Protein Science Laboratory of Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Li
Xiang
X
Qi
Jingjing
J
Wang
Jialu
J
Liu
Xingfeng
X
Zhang
Haiwen
H
Lin
Sheng-Cai
SC
Meng
Anming
A
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002460:Cell Line; D004627:Embryonic Induction; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C492594:dact2 protein, zebrafish; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I