Jiang Jin
University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.
Curr Top Dev Biol. 2017;123:303-329. doi: 10.1016/bs.ctdb.2016.09.002. Epub 2016 Oct 26.
The casein kinase 1 (CK1) family of serine (Ser)/threonine (Thr) protein kinases participates in a myriad of cellular processes including developmental signaling. Hedgehog (Hh) and Wnt pathways are two major and evolutionarily conserved signaling pathways that control embryonic development and adult tissue homeostasis. Deregulation of these pathways leads to many human disorders including birth defects and cancer. Here, I review the role of CK1 in the regulation of Hh and Wnt signal transduction cascades from the membrane reception systems to the transcriptional effectors. In both Hh and Wnt pathways, multiple CK1 family members regulate signal transduction at several levels of the pathways and play either positive or negative roles depending on the signaling status, individual CK1 isoforms involved, and the specific substrates they phosphorylate. A common mechanism underlying the control of CK1-mediated phosphorylation of Hh and Wnt pathway components is the regulation of CK1/substrate interaction within large protein complexes. I will highlight this feature in the context of Hh signaling and draw interesting parallels between the Hh and Wnt pathways.
丝氨酸（Ser）/苏氨酸（Thr）蛋白激酶的酪蛋白激酶1（CK1）家族参与了包括发育信号传导在内的众多细胞过程。刺猬因子（Hh）和Wnt信号通路是两个主要的且在进化上保守的信号通路，它们控制胚胎发育和成年组织的稳态。这些信号通路失调会导致包括出生缺陷和癌症在内的许多人类疾病。在此，我综述了CK1在从膜受体系统到转录效应器的Hh和Wnt信号转导级联调控中的作用。在Hh和Wnt信号通路中，多个CK1家族成员在信号通路的多个层面调控信号转导，其作用取决于信号状态、所涉及的单个CK1亚型以及它们磷酸化的特定底物，发挥正向或负向作用。CK1介导的Hh和Wnt信号通路成分磷酸化调控的一个共同机制是在大型蛋白质复合物中对CK1/底物相互作用的调控。我将在Hh信号传导的背景下突出这一特征，并阐述Hh和Wnt信号通路之间有趣的相似之处。
