title: Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
abstract: PKD1 and PKD2 are two recently identified genes that are responsible for the vast majority of autosomal polycystic kidney disease, a common inherited disease that causes progressive renal failure. PKD1 encodes polycystin, a large glycoprotein that contains several extracellular motifs indicative of a role in cell-cell or cell-matrix interactions, and the PKD2 encodes a protein with homology to a voltage-activated calcium channel and to PKD1. It is currently unknown how mutations of either protein functionally cause autosomal polycystic kidney disease. We show that PKD1 and PKD2 interact through their C-terminal cytoplasmic tails. This interaction resulted in an up-regulation of PKD1 but not PKD2. Furthermore, the cytoplasmic tail of PKD2 but not PKD1 formed homodimers through a coiled-coil domain distinct from the region required for interaction with PKD1. These interactions suggest that PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis and that PKD1 may require the presence of PKD2 for stable expression.
authors.affiliation: Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tsiokas
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Arnould
authors.forename: V P
authors.initials: VP
authors.lastname: Sukhatme
authors.forename: G
authors.initials: G
authors.lastname: Walz
mesh_terms: D019281:Dimerization; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D050396:TRPP Cation Channels
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D011994:Recombinant Proteins; D050396:TRPP Cation Channels