EPS8 explained

Epidermal growth factor receptor kinase substrate 8 is an enzyme that in humans is encoded by the EPS8 gene.^{[1] [2]}

Function

This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.^[2]

Clinical significance

Mutations in EPS8 cause congenital deafness.Behlouli A, Bonnet C, Abdi S, Bouaita A, Lelli A, Hardelin JP, Schietroma C, Rous Y, Louha M, Cheknane A, Lebdi H, Boudjelida K, Makrelouf M, Zenati A, Petit C . EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness . Orphanet Journal of Rare Diseases . 9 . 1 . 55 . 2014 . 24741995 . 4022326 . 10.1186/1750-1172-9-55 . free .

Interactions

EPS8 has been shown to interact with:

• ABI1,^{[3] [4]}
• BAIAP2,^{[5] [6]}
• DVL1,^[7]
• SHB,^[8]
• SHC1^[9]
• SOS1,^{[10] [11]} and
• Src.^[12]

Further reading

• Di Fiore PP, Scita G . Eps8 in the midst of GTPases . Int. J. Biochem. Cell Biol. . 34 . 10 . 1178–83 . 2002 . 12127568 . 10.1016/S1357-2725(02)00064-X .
• Cardwell C . Student or worker? International Meeting of Student Nurses (European Group) . Nursing Mirror and Midwives Journal . 143 . 19 . 38 . 1977 . 1049958 .
• Castagnino P, Biesova Z, Wong WT, Fazioli F, Gill GN, Di Fiore PP . Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent . Oncogene . 10 . 4 . 723–9 . 1995 . 7532293 .
• Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Claesson-Welsh L, Welsh M . Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins . Oncogene . 10 . 8 . 1475–83 . 1995 . 7537362 .
• Avantaggiato V, Torino A, Wong WT, Di Fiore PP, Simeone A . Expression of the receptor tyrosine kinase substrate genes eps8 and eps15 during mouse development . Oncogene . 11 . 6 . 1191–8 . 1995 . 7566980 .
• Matoskova B, Wong WT, Salcini AE, Pelicci PG, Di Fiore PP . Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation . Mol. Cell. Biol. . 15 . 7 . 3805–12 . 1995 . 7791787 . 230619 . 10.1128/MCB.15.7.3805.
• Fazioli F, Minichiello L, Matoska V, Castagnino P, Miki T, Wong WT, Di Fiore PP . Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals . EMBO J. . 12 . 10 . 3799–808 . 1993 . 8404850 . 413663 . 10.1002/j.1460-2075.1993.tb06058.x.
• Matòsková B, Wong WT, Seki N, Nagase T, Nomura N, Robbins KC, Di Fiore PP . RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain . Oncogene . 12 . 12 . 2563–71 . 1996 . 8700515 .
• Matòsková B, Wong WT, Nomura N, Robbins KC, Di Fiore PP . RN-tre specifically binds to the SH3 domain of eps8 with high affinity and confers growth advantage to NIH3T3 upon carboxy-terminal truncation . Oncogene . 12 . 12 . 2679–88 . 1996 . 8700527 .
• Biesova Z, Piccoli C, Wong WT . Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth . Oncogene . 14 . 2 . 233–41 . 1997 . 9010225 . 10.1038/sj.onc.1200822 . free .
• Kishan KV, Scita G, Wong WT, Di Fiore PP, Newcomer ME . The SH3 domain of Eps8 exists as a novel intertwined dimer . Nat. Struct. Biol. . 4 . 9 . 739–43 . 1997 . 9303002 . 10.1038/nsb0997-739 . 36865189 .
• Maa MC, Lai JR, Lin RW, Leu TH . Enhancement of tyrosyl phosphorylation and protein expression of eps8 by v-Src . Biochim. Biophys. Acta . 1450 . 3 . 341–51 . 1999 . 10395945 . 10.1016/S0167-4889(99)00069-5 . free .
• Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegård M, Betsholtz C, Di Fiore PP . EPS8 and E3B1 transduce signals from Ras to Rac . Nature . 401 . 6750 . 290–3 . 1999 . 10499589 . 10.1038/45822 . 1999Natur.401..290S . 205045006 .
• Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, Di Fiore PP . The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5 . Nature . 408 . 6810 . 374–7 . 2000 . 11099046 . 10.1038/35042605 . 2000Natur.408..374L . 4405293 .
• Ion A, Crosby AH, Kremer H, Kenmochi N, Van Reen M, Fenske C, Van Der Burgt I, Brunner HG, Montgomery K, Kucherlapati RS, Patton MA, Page C, Mariman E, Jeffery S . Detailed mapping, mutation analysis, and intragenic polymorphism identification in candidate Noonan syndrome genes MYL2, DCN, EPS8, and RPL6 . J. Med. Genet. . 37 . 11 . 884–6 . 2000 . 11185075 . 1734479 . 10.1136/jmg.37.11.884 .
• Scita G, Tenca P, Areces LB, Tocchetti A, Frittoli E, Giardina G, Ponzanelli I, Sini P, Innocenti M, Di Fiore PP . An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine . J. Cell Biol. . 154 . 5 . 1031–44 . 2001 . 11524436 . 2196181 . 10.1083/jcb.200103146 .

Notes and References

1. Wong WT, Carlomagno F, Druck T, Barletta C, Croce CM, Huebner K, Kraus MH, Di Fiore PP . Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24 . Oncogene . 9 . 10 . 3057–61 . October 1994 . 8084614 .
2. Web site: Entrez Gene: EPS8 epidermal growth factor receptor pathway substrate 8.
3. Biesova Z, Piccoli C, Wong WT . Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth . Oncogene . 14 . 2 . 233–41 . January 1997 . 9010225 . 10.1038/sj.onc.1200822 . free .
4. Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, Di Fiore PP . The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5 . Nature . 408 . 6810 . 374–7 . November 2000 . 11099046 . 10.1038/35042605 . 2000Natur.408..374L . 4405293 .
5. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
6. Funato Y, Terabayashi T, Suenaga N, Seiki M, Takenawa T, Miki H . IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness . Cancer Res. . 64 . 15 . 5237–44 . August 2004 . 15289329 . 10.1158/0008-5472.CAN-04-0327 . 9844872 .
7. Inobe M, ((Katsube Ki)), Miyagoe Y, ((Nabeshima Yi)), Takeda S . Identification of EPS8 as a Dvl1-associated molecule . Biochem. Biophys. Res. Commun. . 266 . 1 . 216–21 . December 1999 . 10581192 . 10.1006/bbrc.1999.1782 .
8. Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Claesson-Welsh L, Welsh M . Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins . Oncogene . 10 . 8 . 1475–83 . April 1995 . 7537362 .
9. Matoskova B, Wong WT, Salcini AE, Pelicci PG, Di Fiore PP . Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation . Mol. Cell. Biol. . 15 . 7 . 3805–12 . July 1995 . 7791787 . 230619 . 10.1128/mcb.15.7.3805.
10. Offenhäuser N, Borgonovo A, Disanza A, Romano P, Ponzanelli I, Iannolo G, Di Fiore PP, Scita G . The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway . Mol. Biol. Cell . 15 . 1 . 91–8 . January 2004 . 14565974 . 307530 . 10.1091/mbc.E03-06-0427 .
11. Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegård M, Betsholtz C, Di Fiore PP . EPS8 and E3B1 transduce signals from Ras to Rac . Nature . 401 . 6750 . 290–3 . September 1999 . 10499589 . 10.1038/45822 . 1999Natur.401..290S . 205045006 .
12. Maa MC, Lai JR, Lin RW, Leu TH . Enhancement of tyrosyl phosphorylation and protein expression of eps8 by v-Src . Biochim. Biophys. Acta . 1450 . 3 . 341–51 . July 1999 . 10395945 . 10.1016/s0167-4889(99)00069-5. free .