Structures of Src-family tyrosine kinases.
The crystal structures of three Src-family tyrosine kinases have been determined recently. The structure of the catalytic domain of Lck has been determined in the active autophosphorylated state. The structures of larger constructs of c-Src and Hck, containing the SH3, SH2 and catalytic domains, as well as a C-terminal regulatory tail, have been determined in the down-regulated state, phosphorylated in the C-terminal tail. A comparison of these structures leads to an unanticipated mechanism for the regulation of catalytic activity by cooperative interactions between the SH2, SH3 and catalytic domains.
Sicheri
F
F
Laboratory of Molecular Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA. Sicheri@rockvax.rockefeller.edu
Kuriyan
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation / Q000502:physiology; D006860:Hydrogen Bonding; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D051572:Proto-Oncogene Proteins c-hck; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry* / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051572:Proto-Oncogene Proteins c-hck; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases