Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2

L Tsiokas, E Kim, T Arnould… - Proceedings of the …, 1997 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
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 …
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.
National Acad Sciences