title: Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations.
abstract: 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 μ- 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.
authors.forename: Hyunho
authors.initials: H
authors.lastname: Kim
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kang
authors.forename: Ah-ra
authors.initials: AR
authors.lastname: Ko
authors.forename: Hayne Cho
authors.initials: HC
authors.lastname: Park
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002154:Calpain / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D059748:Proteolysis; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: D002154:Calpain; D048049:Extracellular Signal-Regulated MAP Kinases; D053614:Janus Kinase 2; D050396:TRPP Cation Channels; C507924:JAK2 protein, human