Pramanik Kallal, Chun Chang Zoon, Garnaas Maija K, Samant Ganesh V, Li Keguo, Horswill Mark A, North Paula E, Ramchandran Ramani
Department of Pediatrics, Children's Research Institute Developmental Vascular Biology Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Blood. 2009 Jan 29;113(5):1184-91. doi: 10.1182/blood-2008-06-162180. Epub 2008 Oct 16.
Mitogen-activated protein kinases play an integral role in several cellular processes. To regulate mitogen-activated protein kinases, cells express members of a counteracting group of proteins called phosphatases. In this study, we have identified a specific role that one member of this family of phosphatases, dual-specific phosphatase-5 (Dusp-5) plays in vascular development in vivo. We have determined that dusp-5 is expressed in angioblasts and in established vasculature and that it counteracts the function of a serine threonine kinase, Snrk-1, which also plays a functional role in angioblast development. Together, Dusp-5 and Snrk-1 control angioblast populations in the lateral plate mesoderm with Dusp-5 functioning downstream of Snrk-1. Importantly, mutations in dusp-5 and snrk-1 have been identified in affected tissues of patients with vascular anomalies, implicating the Snrk-1-Dusp-5 signaling pathway in human disease.
丝裂原活化蛋白激酶在多个细胞过程中发挥着不可或缺的作用。为了调节丝裂原活化蛋白激酶，细胞会表达一组起拮抗作用的蛋白质成员，即磷酸酶。在本研究中，我们确定了该磷酸酶家族的一个成员——双特异性磷酸酶5（Dusp-5）在体内血管发育中所起的特定作用。我们已经确定dusp-5在成血管细胞和已形成的脉管系统中表达，并且它能拮抗丝氨酸苏氨酸激酶Snrk-1的功能，而Snrk-1在成血管细胞发育中也发挥着功能作用。Dusp-5和Snrk-1共同控制侧板中胚层的成血管细胞群体，其中Dusp-5在Snrk-1的下游发挥作用。重要的是，在患有血管异常的患者的受影响组织中已发现dusp-5和snrk-1的突变，这表明Snrk-1-Dusp-5信号通路与人类疾病有关。
