The Structure of PI3K: Difference between revisions

Class IA PI3Ks are tightly associated with a 85 kDa regulatory subunit called p85.<ref name="Wymann"/> P85 contains a Src homology 3 (SH3) domain, a breakpoint-cluster region homology (BH) domain between two proline-rich regions, and two C-terminal SH2 domains separated by an inter-SH2 (iSH2) region, which tightly binds p85 to the catalytic subunit.<ref>PMID:1707345</ref> Since PI3K has multiple protein-interaction domains, p85 is able to interact with several signaling molecules simultaneously, allowing for significant fine tuning of PI3K activity. <ref name="Wymann"/>

<scene name='User:David_Canner/Sandbox_P/Sh2_open/1'>PI3K has two SH2 domains</scene>, an N-terminal (nSH2) domain and a C-terminal (CSH2) domain. <ref name="Flip"/> Both domains recognize similar consensus phosphorylated tyrosine motifs with the pattern: pY-V-X-M in activated receptors and adaptor proteins like PDGF, erbB3, c-Kit and CSF-1 receptors. <ref name="Weber">PMID:11123912</ref> It is upon the interaction of receptor and SH2 domain that the heterodimeric PI3K complex is activated. <ref name="Miled"/> The <scene name='User:David_Canner/Sandbox_P/Sh2/2'>docking site for receptor in NSH2 is defined by the conserved residues Arg 340, Arg 358, and Thr 371</scene> ([[2iui]]), all of which coordinate the phosphorylated tyrosoine phosphate group.<ref name="Nolte"> PMID:8599763</ref> nSH2 was found to interact with the catalytic subunit directly, forming a broad-based scaffold for p110α and coordinates communication between the interacting domains. (Discussed Below). <ref name="Amzel"/>