Phosphoinositide-3-kinases (PI3K) catalyze the phosphorylation of phosphoinosite-4,5-bisphosphate
(PIP2) to produce PIP3 (Fruman et al., 1998). As such, these enzymes are key players in theinitiation of cellular responses to extracellular signals. Class IA PI3K enzymes are activated by binding
phosphorylated tyrosine residues present in activated tyrosine-kinase receptors or their phosphorylated
substrates. Understanding the molecular mechanism of the 2- to 4-fold activation of PI3Ka, a class
I A PI3K, by phosphotyrosine motifs of activated receptor tyrosine kinases is a key step in the characterization
of this important signaling activity