Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a new high-density peptide chip technology that allows probing the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique we have experimentally identified thousands of putative SH2- peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2 mediated probabilistic interaction network, which we make available as a community resource in the PepSpotDB database. A new predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the ERK activation loop was validated by experiments in living cells.

Comments

Cell Rep. Author manuscript; available in PMC Jul 25, 2014. Published in final edited form as: Cell Rep. Apr 25, 2013; 3(4): 1293–1305. Published online Mar 28, 2013. doi: 10.1016/j.celrep.2013.03.001 PMCID: PMC4110347 NIHMSID: NIHMS604676

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