Engineering Commons^™

Computational Models Of Tandem Src Homology 2 Domain Interactions And Application To Phosphoinositide 3-Kinase, Dipak Barua, James R. Faeder, Jason M. Haugh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Intracellular signal transduction proteins typically utilize multiple interaction domains for proper targeting, and thus a broad diversity of distinct signaling complexes may be assembled. Considering the coordination of only two such domains, as in tandem Src homology 2 (SH2) domain constructs, gives rise to a kinetic scheme that is not adequately described by simple models used routinely to interpret in vitro binding measurements. To analyze the interactions between tandem SH2 domains and bisphosphorylated peptides, we formulated detailed kinetic models and applied them to the phosphoinositide 3-kinase p85 regulatory subunit/platelet-derived growth factor β-receptor system. Data for this system from different in …