The catalytic domain of protein tyrosine kinases can interconvert between active and inactive conformations in response to regulatory inputs. We recently demonstrated that Src kinase features an allosteric network that couples substrate-binding sites. However, the extent of conformational and dynamic changes that are propagated throughout the kinase domain remains poorly understood. Here, we monitor by NMR the effect of conformationally selective inhibitors on kinase backbone dynamics. We find that inhibitor binding and activation loop autophosphorylation induces dynamic changes across the entire kinase. We identify a highly conserved amino acid, Gly449, that is necessary for Src activation. Finally, we show for the first time how the SH3-SH2 domains perturb the dynamics of the kinase domain in the context of the full length protein. We provide experimental support for long-range communication in Src kinase that leads to the relative stabilization of active or inactive conformations and modulation of substrate affinity.