Binding and function of phosphotyrosines of the Ephrin A2 (EphA2) receptor using synthetic Sterile {alpha} Motif (SAM) domains [Signal Transduction]

May 13th, 2014 by Borthakur, S., Lee, H., Kim, S., Wang, B.-C., Buck, M.

The Sterile α Motif (SAM) domain of the ephrin receptor tyrosine kinase, EphA2, undergoes tyrosine phosphorylation; but the effect of phosphorylation on the structure and interactions of the receptor is unknown. Studies to address these questions have been hindered by the difficulty to obtain site specifically phosphorylated proteins in adequate amounts. Here, we describe the use of chemically synthesized and specifically modified domain-length peptides to study the behavior of phosphorylated EphA2 SAM domains. We show that tyrosine phosphorylation of any of the three tyrosines, Y921, Y930, and Y960 have a surprisingly small effect on the EphA2 SAM structure and stability. However, phosphorylation at Y921 and Y930 enables differential binding to the SH2 domain of the adaptor protein Grb7, which we propose will lead to distinct functional outcomes. Setting up different signaling platforms defined by selective interactions with the adaptor proteins thus adds another level of regulation to EphA2 signaling.
  • Posted in Journal of Biological Chemistry, Publications
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