Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

详细信息    查看全文

• 作者：Hyunho Kim ; Ah-Young Kang ; Ah-ra Ko ; Hayne Cho Park ; Insuk So ; Jong Hoon Park ; Hae Il Cheong ; Young-Hwan Hwang ; Curie Ahn
• 关键词：ADPKD ; autosomal dominant polycystic kidney disease ; PC1 ; polycystin-1 ; PC2 ; polycystin-2 ; CT ; C-terminal ; JAK ; Janus kinase ; STAT ; signal transducer and activator of transcription ; TRP ; transient receptor potential ; HA ; haemagglutinin ; PKD ; polycystic kidney disease ; ERK ; extracellular signal-regulated kinase ; mTOR ; mammalian target of rapamycin
• 刊名：Experimental Cell Research
• 出版年：1 January, 2014
• 年：2014
• 卷：320
• 期：1
• 页码：62-68
• 全文大小：1061 K

文摘

Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for 渭- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration.