The Structure of PI3K: Difference between revisions

==Adapter Subunit==

===The p85 Adapter Subunit===

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"> PMID: 9838078</ref>

All PI3K catalytic subunits possess intrinsic protein serine kinase activity. PI3K regulatory subunits can be phophorylated by the catalytic subunit (p110) at specific sites. For example, phophorylation of Ser 608, a residue located in an area of the iSH2 domain that is critical for PIP2 presentation to the catalytic subunit, results in a dramatic reduction in PI3K lipid kinase activity.<ref>PMID: 8313897</ref> Additionally, tyrosines 580 and 607 can be phosphorylated upon stimulation with insulin and growth factor along with <scene name='User:David_Canner/Sandbox_P/Tyr_508/1'>Tyr 508 upon PDGF receptor mediation</scene>. <ref name="Wymann"/> Phosphorylation of Tyr 688 in the CSH2 domain by Abl and Lck results in reduced affinity for phosphopeptides and subsequent activation of the catalytic domain. <ref>PMID:9461588 </ref>

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==The Catalytic Subunit==