The impact of the interaction between Embryonic stem cell-expressed Ras and Arginase-1 in hepatic stellate cells

Embryonic stem cell-expressed Ras (ERAS) represents a unusual member of the Ras family with remarkable characteristics in quiescent hepatic stellate cells (HSC).1 ERAS contains a unique N-terminal extension (38 amino acids) upstream of its guanosine triphosphate binding domain, which exhibits remarkable sequence deviations between human and rat species. However, the function of such an additional region with various motifs [1], which is not found in other classical Ras proteins (e.g., HRAS, KRAS and NRAS), remained unclear. Comparative proteome analysis revealed that ERAS is associated with 51 proteins (10 with the human ERAS, 3 with rat ERAS and 38 with both species), participating in various cellular processes, including cell cycle, transcription, immune response, signal transduction, cell adhesion, cytoskeletal dynamics and metabolism. The cytosolic Arginase-1 is one of these proteins, which is well-known to convert L-arginine to L-ornithine. Protein-protein interaction studies have shown that Arginase-1 physically binds to different ERAS variants, including isolated ERAS N-terminus, under cell-free condition using purified proteins. Preliminary results on deciphering new mechanisms controlling the ERAS signal transduction in quiescent HSC, including the interaction between ERAS and Arginase-1 will be discussed.

[1] Nakhaei-Rad, S., Nakhaeizadeh, H., Kordes, C., Cirstea, I. C., Schmick, M., Dvorsky, R., Bastiaens, P. I., Haussinger, D. &Ahmadian, M. R. (2015). The function of embryonic stem cell-expressed Ras (E-Ras), a unique Ras family member, correlates with its additional motifs and its structural properties. J Biol Chem 290:15892 – 15903

Corresponding author: Ahmadian, Mohammad Reza

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