Interaction of the molecular weight 85K regulatory subunit of the phosphatidylinositol 3-kinase with the insulin receptor and the insulin-like growth factor-1 (IGF- I) receptor: comparative study using the yeast two-hybrid system
Abstract
Activation of the phosphatidyl inositol 3-kinase (PI 3-kinase) is one of the immediate events in signaling by the insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-IR). The IR and IGF-IR are two closely related tyrosine kinases, which are activated on binding of their respective ligands. Previous studies have proposed that the two receptors interact directly with the SH2 domains of the Mr 85K regulatory subunit (p85) of PI 3- kinase via phosphorylated Y1322THM and Y1316AHM sequences located in the carboxyl-terminal domain of the IR and the IGF-IR, respectively. We In this study we have used the yeast two-hybrid system to compare the interaction of the cytoplasmic domains of the IR and the IGF-IR with p85. We found that the IR is more efficient in interacting with the p85 than is the IGF-IR. For both receptors, deletion of the region containing the Y1322THM sequence in the IR and the Y1316AHM-similar sequence in the IGF-IR decreases their ability to interact with p85. However, these mutated receptors still interacted with the full-length p85, suggesting that other regions in the receptors might be involved in the interaction. Furthermore, mutations of the three major autophosphorylation sites indicate that...Continue Reading
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