High impact information on Eps15

• Using an EH domain-specific probe derived from the eps15 cDNA, we cloned and characterized a cDNA encoding an EH-containing protein with overall similarity to Eps15; we designated this protein Eps15r (for Eps15-related) [1].
• Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins [1].
• This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heterogeneous proteins of yeast and nematode [1].
• A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution [1].
• In neurons, L1 is endocytosed preferentially at the rear of axonal growth cones, colocalizing with Eps15, another marker for the clathrin endocytic pathway [2].

Biological context of Eps15

• Eps15, a phosphorylation substrate of the epidermal growth factor (EGF) receptor kinase, has been shown to bind to the alpha-subunit of the clathrin-associated protein complex AP-2 [3].
• Upon over-expression, the ubiquitin-interacting motif abrogated the capacity of c-Cbl to promote EGF receptor endocytosis and only allowed receptor internalization via a route that lacked Eps15 [4].
• Differential patterns of expression of Eps15 and Eps15R during mouse embryogenesis [5].
• Hrs also associates with proteins implicated in endocytosis and exocytosis such as SNAP-25 and Eps15 [6].

Anatomical context of Eps15

• Here we report that in cells, virtually all Eps15 interacts with the cytosol and membrane-bound forms of AP-2 [3].
• Unexpectedly, Eps15 was found at the edge of forming coated pits and at the rim of budding coated vesicles [3].
• Indeed, EGF-induced redistribution of Eps15 to the plasma membrane and endosomes depended on its ubiquitin-interacting motif [4].
• Eps15 and Eps15R are related tyrosine kinase substrates, which have been implicated in endocytosis and synaptic vesicle recycling [5].
• In other tissues, Eps15 was first seen in the liver primordium and at low levels in choroid plexus, lung, kidney and intestine; later on the expression was maintained at high levels in epithelia [5].

Physical interactions of Eps15

• c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15 [4].

Other interactions of Eps15

• The most striking difference was at the level of subcellular localization, with Eps15 present in the cytosol and on the plasma membrane, while Eps15R exhibited mainly a nuclear localization [5].
• This suggested that ubiquitin provides a direct or indirect link between the receptor and Eps15 [4].
• We show here that both rat epsin and Eps15 are mitotic phosphoproteins and that their mitotic phosphorylation inhibits binding to the appendage domain of alpha-adaptin [7].
• This newly identified protein contains an Eps homology (EH) domain, which was first detected in the epidermal growth factor (EGF) receptor substrate Eps15 [8].
• 1H, 15N, and 13C NMR resonance assignments for the Eps15 homology domain of Reps1 [9].

Analytical, diagnostic and therapeutic context of Eps15

• Immunofluorescence microscopy reveals nearly absolute co-localization of Eps15 with AP-2 and clathrin, and analysis by immunoelectron microscopy shows that the localization of membrane-associated Eps15 is restricted to the profiles corresponding to endocytic coated pits and vesicles [3].

References