Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase.

Pyk2 is a multi-domain non-receptor tyrosine kinase that serves dual roles as a signaling enzyme and scaffold. Pyk2 activation involves a multi-stage cascade of conformational rearrangements and protein interactions initiated by autophosphorylation of a linker site. Linker phosphorylation recruits Src kinase, and Src-mediated phosphorylation of the Pyk2 activation loop confers full activation.

Activation loop phosphorylation tunes conformational dynamics underlying Pyk2 tyrosine kinase activation.

Pyk2 is a multidomain non-receptor tyrosine kinase that undergoes a multistage activation mechanism. Activation is instigated by conformational rearrangements relieving autoinhibitory FERM domain interactions. The kinase autophosphorylates a central linker residue to recruit Src kinase.

Controlling Kinase Activities by Selective Inhibition of Peptide Substrates.

Phosphorylation is the most common reversible post-translational modification (PTM) of proteins. Because a given kinase often has many substrates in a cell and is involved in numerous functions, traditional inhibition of the enzyme leads to unintended consequences. Here we report synthetic receptors to manipulate kinase phosphorylation precisely for the first time, utilizing the receptors' abilities to bind peptides with high affinity and specificity.