Dynamic steps in receptor tyrosine kinase mediated activation of class IA phosphoinositide 3-kinases (PI3K) captured by H/D exchange (HDX-MS).

ABSTRACT: The catalytic subunits of all class IA phosphoinositide 3-kinases (PI3Ks) associate with identical p85-related subunits and phosphorylate PIP2 yielding PIP3, but they can vary greatly in the signaling pathways in which they participate. The binding of the p85 subunit to the p110 catalytic subunits is constitutive, and this inhibits activity, but some of the inhibitory contacts are reversible and subject to regulation. Interaction with phosphotyrosine-containing peptides (RTK-pY) releases a subset of these inhibitory contacts. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) provides a map of the dynamic interactions unique to each of the isotypes. RTK-pY binding exposes the p110 helical domains for all class IA enzymes (due to release of the nSH2 contact) and exposes the C-lobe of th

SUBMITTER: Burke JE 

PROVIDER: S-EPMC3613897 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature