The Tec family kinase Itk exists as a folded monomer in vivo.
Tec family tyrosine kinases transduce signals from antigen and other receptors. In particular, Itk plays an important role in T-cell development and activation. Itk has an N-terminal pleckstrin homology domain, a Tec Homology domain with a proline-rich region, SH3 and SH2 domains and a kinase domain, the structure each of which has been determined. However, the full structure of Itk and other Tec kinases remain elusive. Models of Itk suggest either a head to tail dimer, with the SH2 domain interacting with the SH3 domain, or a folded monomer with the SH3 domain interacting with the proline-rich region. We show here that in vivo Itk exists as a monomer, with the pleckstrin homology domain less than 80 A from the C terminus. Zn2+ coordinating residues in the Tec Homology domain, not the proline-rich region, are critical for this intramolecular interaction. These data have implications for our understanding of Tec family kinase structure.
Qi
Qian
Q
Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
August
Avery
A
D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D017510:Protein Folding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains / Q000502:physiology
C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D015032:Zinc