Epidermal growth factor receptor substrate

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Human Eps8 SH3 domino (cyan, green) complex with TS33 secreted effector NleH homolog peptide (pink, yellow) (PDB code 7tzk)

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Function

Epidermal growth factor receptor substrate 8 (Eps8) is a substrate for receptor tyrosine kinases^[1]. Eps8 i overexpressed in human pituitary tumors^[2]. Eps8 has a role in amplifying growth factor signaling in human pituitary tumors to promote proliferation and cell survival. Eps8 enable actin binding activity and small GTPase binding activity. The actin bundling activity of Eps8 is hindered by its phosphorylation by kinase.
Epidermal growth factor receptor substrate 15 (Eps15) is a component of the endocytic machinery. Eps15 structur is comprised of N-terminal which contains 3 SH3 domains, a central coiled-coil region and a C-terminal region containing multiple copies of Asp-Pro-Phe^[3].
See also Epidermal growth factor and Epidermal Growth Factor Receptor.

Disease

Eps8 promotes cervical cancer metastasis^[4].

Relevance

Eps8 overexpressing cells are protected from serum withdrawal-induced apoptosis.

Structural highlights

The 3D structure of the complex between Eps8 SH3 domain and the kinase NleH peptide shows the interaction of the PxxDY motif with Eps8 via multiple hydrogen bonds^[5] (7tzk). The water molecules are shown as red spheres. The C-terminal SAM domain of Eps8 contains the actin binding motif LNK (2e8m) and the phosphorylated Ser residue.