Controlling the activity of the Tec kinase Itk by mutation of the phenylalanine gatekeeper residue.

ABSTRACT: The regulatory spine is a set of conserved residues that are assembled and disassembled upon activation and inactivation of kinases. We recently identified the regulatory spine within the immunologically important Tec family kinases and have shown that in addition to the core spine residues within the kinase domain itself, contributions from the SH2-kinase linker region result in an extended spine structure for this kinase family. Disruption of the regulatory spine, either by mutation or by removal of the amino-terminal SH2-kinase linker region or by mutation of core spine residues, leads to inactivation of the Tec kinases. With a focus on the Tec family members, Itk and Btk, we now show that the gatekeeper residue is also critical for the assembly of the regulatory spine. Mutation of the

SUBMITTER: Joseph RE 

PROVIDER: S-EPMC3083488 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature