Plakophilin-4 Explained

Plakophilin-4 is a protein that in humans is encoded by the PKP4 gene.^{[1] [2] [3]}

Function

Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants have been found for this gene, but the full-length nature of only two of them have been described so far. These two variants encode distinct isoforms.^[3]

Interactions

PKP4 has been shown to interact with:

• Erbin,^{[4] [5] [6]}
• PDZD2,^{[7] [8]} and
• PSEN1.^[9]

Further reading

• Keil R, Wolf A, Hüttelmaier S, Hatzfeld M . Beyond regulation of cell adhesion: local control of RhoA at the cleavage furrow by the p0071 catenin. . Cell Cycle . 6 . 2 . 122–7 . 2007 . 17264675 . 10.4161/cc.6.2.3741 . free .
• Bonné S, van Hengel J, van Roy F . Chromosomal mapping of human armadillo genes belonging to the p120(ctn)/plakophilin subfamily. . Genomics . 51 . 3 . 452–4 . 1998 . 9721216 . 10.1006/geno.1998.5398 .
• Levesque G, Yu G, Nishimura M, Zhang DM, Levesque L, Yu H, Xu D, Liang Y, Rogaeva E, Ikeda M, Duthie M, Murgolo N, Wang L, VanderVere P, Bayne ML, Strader CD, Rommens JM, Fraser PE, St George-Hyslop P . Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin. . J. Neurochem. . 72 . 3 . 999–1008 . 1999 . 10037471 . 10.1046/j.1471-4159.1999.0720999.x . 36124450 . free .
• Stahl B, Diehlmann A, Südhof TC . Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071. . J. Biol. Chem. . 274 . 14 . 9141–8 . 1999 . 10092585 . 10.1074/jbc.274.14.9141 . free .
• Deguchi M, Iizuka T, Hata Y, Nishimura W, Hirao K, Yao I, Kawabe H, Takai Y . PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071. . J. Biol. Chem. . 275 . 38 . 29875–80 . 2000 . 10896674 . 10.1074/jbc.M005384200 . free .
• Schröder R, van der Ven PF, Warlo I, Schumann H, Fürst DO, Blümcke I, Schmidt MC, Hatzfeld M . p0071, a member of the armadillo multigene family, is a constituent of sarcomeric I-bands in human skeletal muscle. . J. Muscle Res. Cell. Motil. . 21 . 6 . 577–86 . 2001 . 11206135 . 10.1023/A:1026587530656 . 1342967 .
• Jaulin-Bastard F, Arsanto JP, Le Bivic A, Navarro C, Vély F, Saito H, Marchetto S, Hatzfeld M, Santoni MJ, Birnbaum D, Borg JP . Interaction between Erbin and a Catenin-related protein in epithelial cells. . J. Biol. Chem. . 277 . 4 . 2869–75 . 2002 . 11711544 . 10.1074/jbc.M109652200 . free .
• Izawa I, Nishizawa M, Tomono Y, Ohtakara K, Takahashi T, Inagaki M . ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells. . Genes Cells . 7 . 5 . 475–85 . 2002 . 12047349 . 10.1046/j.1365-2443.2002.00533.x . 12598418 . free .
• Ohno H, Hirabayashi S, Iizuka T, Ohnishi H, Fujita T, Hata Y . Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells. . Oncogene . 21 . 46 . 7042–9 . 2002 . 12370826 . 10.1038/sj.onc.1205852 . free .
• Calkins CC, Hoepner BL, Law CM, Novak MR, Setzer SV, Hatzfeld M, Kowalczyk AP . The Armadillo family protein p0071 is a VE-cadherin- and desmoplakin-binding protein. . J. Biol. Chem. . 278 . 3 . 1774–83 . 2003 . 12426320 . 10.1074/jbc.M205693200 . free .
• Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC . Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. . Proc. Natl. Acad. Sci. U.S.A. . 100 . 2 . 443–8 . 2003 . 12522270 . 141014 . 10.1073/pnas.2436191100 . 2003PNAS..100..443S . free .
• Hatzfeld M, Green KJ, Sauter H . Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains. . J. Cell Sci. . 116 . Pt 7 . 1219–33 . 2003 . 12615965 . 10.1242/jcs.00275 . free .
• Setzer SV, Calkins CC, Garner J, Summers S, Green KJ, Kowalczyk AP . Comparative analysis of armadillo family proteins in the regulation of a431 epithelial cell junction assembly, adhesion and migration. . J. Invest. Dermatol. . 123 . 3 . 426–33 . 2004 . 15304078 . 10.1111/j.0022-202X.2004.23319.x . free .
• Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM . Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. . Mol. Cell. Proteomics . 4 . 9 . 1240–50 . 2005 . 15951569 . 10.1074/mcp.M500089-MCP200 . free .
• Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R . Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. . Nat. Methods . 2 . 8 . 591–8 . 2005 . 16094384 . 10.1038/nmeth776 . 20475874 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .

Notes and References

1. Paffenholz R, Franke WW . Identification and localization of a neurally expressed member of the plakoglobin/armadillo multigene family . Differentiation . 61 . 5 . 293–304 . December 1997 . 9342840 . 10.1046/j.1432-0436.1997.6150293.x .
2. Hatzfeld M, Nachtsheim C . Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins . J Cell Sci . 109 . 11 . 2767–78 . May 1997 . 10.1242/jcs.109.11.2767 . 8937994 .
3. Web site: Entrez Gene: PKP4 plakophilin 4.
4. Izawa I, Nishizawa M, Tomono Y, Ohtakara K, Takahashi T, Inagaki M . ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells . Genes Cells . 7 . 5 . 475–85 . May 2002 . 12047349 . 10.1046/j.1365-2443.2002.00533.x. 12598418 . free .
5. Jaulin-Bastard F, Arsanto JP, Le Bivic A, Navarro C, Vély F, Saito H, Marchetto S, Hatzfeld M, Santoni MJ, Birnbaum D, Borg JP . Interaction between Erbin and a Catenin-related protein in epithelial cells . J. Biol. Chem. . 277 . 4 . 2869–75 . January 2002 . 11711544 . 10.1074/jbc.M109652200 . free .
6. Laura RP, Witt AS, Held HA, Gerstner R, Deshayes K, Koehler MF, Kosik KS, Sidhu SS, Lasky LA . The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF . J. Biol. Chem. . 277 . 15 . 12906–14 . April 2002 . 11821434 . 10.1074/jbc.M200818200 . free .
7. Deguchi M, Iizuka T, Hata Y, Nishimura W, Hirao K, Yao I, Kawabe H, Takai Y . PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071 . J. Biol. Chem. . 275 . 38 . 29875–80 . September 2000 . 10896674 . 10.1074/jbc.M005384200 . free .
8. Ohno H, Hirabayashi S, Iizuka T, Ohnishi H, Fujita T, Hata Y . Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells . Oncogene . 21 . 46 . 7042–9 . October 2002 . 12370826 . 10.1038/sj.onc.1205852 . free .
9. Stahl B, Diehlmann A, Südhof TC . Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071 . J. Biol. Chem. . 274 . 14 . 9141–8 . April 1999 . 10092585 . 10.1074/jbc.274.14.9141. free .