F
IPR039801

Epidermal growth factor receptor kinase substrate 8-like

InterPro entry
Short nameEPS8-like

Description

This entry includes EPS8 and EPS8L1-3 from animals.

Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities
[4]
. It forms a complex with Sos-1, Abi1 and the lipid kinase phosphoinositide 3-kinase (PI3-K) to regulate Rac activation that leads to actin cytoskeletal remodeling
[6]
. It is critical for dendritic cell migration
[4]
. It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells
[2]
. It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF)
[3]
. It has been linked to proliferation, metastasis and prognosis of many malignant tumours
[1]
.

Similarly to EPS8, EPSLs interact with Abi1 and Sos-1. However, only EPS8L1 and EPS8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo
[6]
. Eps8L2 null-mutant mice has been shown to exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology
[5]
.

References

1.[Correlation of Eps8 with proliferation, metastasis and prognosis of malignant tumors]. Sun J, Jin LY, Wang HY, Zhou JQ, Li YJ, He YZ, Li YH. Zhongguo Shi Yan Xue Ye Xue Za Zhi 21, 493-7, (2013). View articlePMID: 23628062

2.The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of Mammalian cochlear outer hair cells. Olt J, Mburu P, Johnson SL, Parker A, Kuhn S, Bowl M, Marcotti W, Brown SD. PLoS ONE 9, e87331, (2014). View articlePMID: 24475274

3.Eps8 regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF). Menna E, Disanza A, Cagnoli C, Schenk U, Gelsomino G, Frittoli E, Hertzog M, Offenhauser N, Sawallisch C, Kreienkamp HJ, Gertler FB, Di Fiore PP, Scita G, Matteoli M. PLoS Biol. 7, e1000138, (2009). View articlePMID: 19564905

4.The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration. Frittoli E, Matteoli G, Palamidessi A, Mazzini E, Maddaluno L, Disanza A, Yang C, Svitkina T, Rescigno M, Scita G. Immunity 35, 388-99, (2011). View articlePMID: 21835647

5.Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2. Furness DN, Johnson SL, Manor U, Ruttiger L, Tocchetti A, Offenhauser N, Olt J, Goodyear RJ, Vijayakumar S, Dai Y, Hackney CM, Franz C, Di Fiore PP, Masetto S, Jones SM, Knipper M, Holley MC, Richardson GP, Kachar B, Marcotti W. Proc. Natl. Acad. Sci. U.S.A. 110, 13898-903, (2013). View articlePMID: 23918390

6.The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway. Offenhauser N, Borgonovo A, Disanza A, Romano P, Ponzanelli I, Iannolo G, Di Fiore PP, Scita G. Mol. Biol. Cell 15, 91-8, (2004). View articlePMID: 14565974

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