| 释义 |
- Function
- Interactions
- References
- Further reading
{{Infobox_gene}}Partitioning defective 6 homolog alpha is a protein that in humans is encoded by the PARD6A gene.[1][2][3] Function This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[3] A recent study shows that Par6 associates with PKC-ι but not with PKC-zeta in melanoma. Oncogenic PKC-iota can promote melanoma cell invasion by up-regulating PKC-ι/Par6 pathway during EMT. PKC-ι inhibition or knockdown resulted an increase E-cadherin and RhoA levels while decreasing total Vimentin, phophorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma.[4] {{Div col end}} Interactions PARD6A has been shown to interact with: - CDC42,[2][5][6]
- ECT2[7]
- Protein kinase Mζ,[2][7][8] and
- RAC1.[2][6]
- Protein kinase C-ι.[9]
{{Div col end}} References 1. ^{{cite journal | vauthors = Rousset R, Fabre S, Desbois C, Bantignies F, Jalinot P | title = The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins | journal = Oncogene | volume = 16 | issue = 5 | pages = 643–54 | date = March 1998 | pmid = 9482110 | pmc = | doi = 10.1038/sj.onc.1201567 }}
2. ^1 2 3 {{cite journal | vauthors = Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H | title = Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C | journal = Genes Cells | volume = 6 | issue = 2 | pages = 107–19 | date = March 2001 | pmid = 11260256 | pmc = | doi = 10.1046/j.1365-2443.2001.00404.x }}
3. ^1 {{cite web | title = Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50855| accessdate = }}
4. ^{{cite journal |vauthors=Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M | title = Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis | journal = Int. J. Oncol. | volume = 51 | issue = 5 | pages = 1370–1382 | year = 2017 | pmid = 29048609 | pmc = 5642393 | doi = 10.3892/ijo.2017.4131 }}
5. ^{{cite journal | vauthors = Joberty G, Petersen C, Gao L, Macara IG | title = The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 | journal = Nat. Cell Biol. | volume = 2 | issue = 8 | pages = 531–9 | date = August 2000 | pmid = 10934474 | doi = 10.1038/35019573 }}
6. ^1 {{cite journal | vauthors = Qiu RG, Abo A, Steven Martin G | title = A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation | journal = Curr. Biol. | volume = 10 | issue = 12 | pages = 697–707 | date = June 2000 | pmid = 10873802 | doi = 10.1016/s0960-9822(00)00535-2}}
7. ^1 {{cite journal | vauthors = Liu XF, Ishida H, Raziuddin R, Miki T | title = Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity | journal = Mol. Cell. Biol. | volume = 24 | issue = 15 | pages = 6665–75 | date = August 2004 | pmid = 15254234 | pmc = 444862 | doi = 10.1128/MCB.24.15.6665-6675.2004 }}
8. ^{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
9. ^{{cite journal |vauthors=Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M | title = Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis | journal = Int. J. Oncol. | volume = 51 | issue = 5 | pages = 1370–1382 | year = 2017 | pmid = 29048609 | pmc = 5642393 | doi = 10.3892/ijo.2017.4131 }}
{{Clear}} Further reading {{Refbegin | 2}}- {{cite journal | vauthors = Solecki DJ, Govek EE, Hatten ME | title = mPar6 alpha controls neuronal migration. | journal = J. Neurosci. | volume = 26 | issue = 42 | pages = 10624–5 | year = 2006 | pmid = 17050699 | doi = 10.1523/JNEUROSCI.4060-06.2006 }}
- {{cite journal | vauthors = Qiu RG, Abo A, Steven Martin G | title = A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. | journal = Curr. Biol. | volume = 10 | issue = 12 | pages = 697–707 | year = 2000 | pmid = 10873802 | doi = 10.1016/S0960-9822(00)00535-2 }}
- {{cite journal | vauthors = Joberty G, Petersen C, Gao L, Macara IG | title = The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. | journal = Nat. Cell Biol. | volume = 2 | issue = 8 | pages = 531–9 | year = 2000 | pmid = 10934474 | doi = 10.1038/35019573 }}
- {{cite journal | vauthors = Johansson A, Driessens M, Aspenström P | title = The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. | journal = J. Cell Sci. | volume = 113 | issue = 18 | pages = 3267–75 | year = 2000 | pmid = 10954424 | doi = }}
- {{cite journal | vauthors = Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, Akimoto K, Izumi Y, Ohnishi T, Ohno S | title = Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. | journal = J. Cell Biol. | volume = 152 | issue = 6 | pages = 1183–96 | year = 2001 | pmid = 11257119 | pmc = 2199212 | doi = 10.1083/jcb.152.6.1183 }}
- {{cite journal | vauthors = Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H | title = PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions. | journal = Biochem. Biophys. Res. Commun. | volume = 299 | issue = 4 | pages = 641–6 | year = 2003 | pmid = 12459187 | doi = 10.1016/S0006-291X(02)02698-0 }}
- {{cite journal | vauthors = Hurd TW, Gao L, Roh MH, Macara IG, Margolis B | title = Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. | journal = Nat. Cell Biol. | volume = 5 | issue = 2 | pages = 137–42 | year = 2003 | pmid = 12545177 | doi = 10.1038/ncb923 }}
- {{cite journal | vauthors = Brajenovic M, Joberty G, Küster B, Bouwmeester T, Drewes G | title = Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. | journal = J. Biol. Chem. | volume = 279 | issue = 13 | pages = 12804–11 | year = 2004 | pmid = 14676191 | doi = 10.1074/jbc.M312171200 }}
- {{cite journal | vauthors = Lemmers C, Michel D, Lane-Guermonprez L, Delgrossi MH, Médina E, Arsanto JP, Le Bivic A | title = CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. | journal = Mol. Biol. Cell | volume = 15 | issue = 3 | pages = 1324–33 | year = 2004 | pmid = 14718572 | pmc = 363137 | doi = 10.1091/mbc.E03-04-0235 }}
- {{cite journal | vauthors = Weyrich P, Kapp K, Niederfellner G, Melzer M, Lehmann R, Häring HU, Lammers R | title = Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis via atypical protein kinase C. | journal = Mol. Endocrinol. | volume = 18 | issue = 5 | pages = 1287–300 | year = 2005 | pmid = 14976222 | doi = 10.1210/me.2003-0253 }}
- {{cite journal | vauthors = Liu XF, Ishida H, Raziuddin R, Miki T | title = Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity. | journal = Mol. Cell. Biol. | volume = 24 | issue = 15 | pages = 6665–75 | year = 2004 | pmid = 15254234 | pmc = 444862 | doi = 10.1128/MCB.24.15.6665-6675.2004 }}
- {{cite journal | vauthors = Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP | title = Phosphoproteomic analysis of the developing mouse brain. | journal = Mol. Cell. Proteomics | volume = 3 | issue = 11 | pages = 1093–101 | year = 2005 | pmid = 15345747 | doi = 10.1074/mcp.M400085-MCP200 }}
- {{cite journal | vauthors = Hirano Y, Yoshinaga S, Takeya R, Suzuki NN, Horiuchi M, Kohjima M, Sumimoto H, Inagaki F | title = Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. | journal = J. Biol. Chem. | volume = 280 | issue = 10 | pages = 9653–61 | year = 2005 | pmid = 15590654 | doi = 10.1074/jbc.M409823200 }}
- {{cite journal | vauthors = Weyrich P, Lammers R, Fritsche A, Machicao F, Häring HU, Stefan N | title = A novel functional polymorphism (-336A/G) in the promoter of the partitioning-defective protein-6alpha gene is associated with increased glucose tolerance and lower concentrations of serum non-esterified fatty acids. | journal = Diabetologia | volume = 48 | issue = 4 | pages = 669–74 | year = 2005 | pmid = 15744531 | doi = 10.1007/s00125-005-1688-4 }}
- {{cite journal | vauthors = Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL | title = Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. | journal = Science | volume = 307 | issue = 5715 | pages = 1603–9 | year = 2005 | pmid = 15761148 | doi = 10.1126/science.1105718 }}
- {{cite journal | vauthors = Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL | title = High-throughput mapping of a dynamic signaling network in mammalian cells. | journal = Science | volume = 307 | issue = 5715 | pages = 1621–5 | year = 2005 | pmid = 15761153 | doi = 10.1126/science.1105776 }}
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