Engineering Commons^™

Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.

Chemical and Biochemical Engineering Faculty Research & Creative Works

Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 …