title: Rock2 controls TGFbeta signaling and inhibits mesoderm induction in zebrafish embryos.
abstract: 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.
authors.affiliation: Protein Science Laboratory of Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qi
authors.forename: Jialu
authors.initials: J
authors.lastname: Wang
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Liu
authors.forename: Haiwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Lin
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: 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*
chemical_list: 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