The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling.
SH2 domains are interaction modules uniquely dedicated to the recognition of phosphotyrosine sites and are embedded in proteins that couple protein-tyrosine kinases to intracellular signaling pathways. Here, we report a comprehensive bioinformatics, structural, and functional view of the human and mouse complement of SH2 domain proteins. This information delimits the set of SH2-containing effectors available for PTK signaling and will facilitate the systems-level analysis of pTyr-dependent protein-protein interactions and PTK-mediated signal transduction. The domain-based architecture of SH2-containing proteins is of more general relevance for understanding the large family of protein interaction domains and the modular organization of the majority of human proteins.
Liu
Bernard A
BA
Ben May Institute for Cancer Research and the Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637.
Jablonowski
Karl
K
Ben May Institute for Cancer Research and the Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637.
Raina
Monica
M
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada.
Arcé
Michael
M
Ben May Institute for Cancer Research and the Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637.
Pawson
Tony
T
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada. Electronic address: pawson@mshri.on.ca.
Nash
Piers D
PD
Ben May Institute for Cancer Research and the Committee on Cancer Biology, The University of Chicago, Chicago, Illinois 60637. Electronic address: pdnash@uchicago.edu.
D000818:Animals; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains / Q000502:physiology*
D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases