Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6965-70.
Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
Tsiokas, L., Kim, E., Arnould, T., Sukhatme, V. P., Walz, G.,
["Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA."]
["Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA."]
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.
PMID: 9192675
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Validation: In vitro validation
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| Assay with recombinant proteins | Reference | |||||||||
| TRP channel construct | Interactor construct | |||||||||
| TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
| TRPP1 |
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PKD1/Polycystin-1 | Yeast two-hybrid | Human | 680-968 | Yeast | Human | 1114-1339 | Yeast | 9192675 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Validation: In vivo validation
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|---|---|---|---|---|---|---|---|---|---|---|
| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP1 |
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PKD1/Polycystin-1 | Co-immunoprecipitation | HEK293T | Human | 680-968 | Human | 1114-1339 | 9192675 | |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
| Characterization
|
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|---|---|---|---|---|---|---|---|---|---|---|
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP1 |
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PKD1/Polycystin-1 | Yeast two-hybrid | Human | 742-968 | Human | 1227-1339 | 9192675 | ||
| TRPP1 |
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PKD1/Polycystin-1 | Co-immunoprecipitation | Human | 680-968 | Human | 1227-1339 | 9192675 | ||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)