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Phosphotyrosine signaling: a prototype for modular protein‐protein interactions
Author(s) -
Pawson Tony
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a4
Subject(s) - protein–protein interaction , proteome , signal transduction , signal transducing adaptor protein , biology , function (biology) , mechanism (biology) , scaffold protein , sh2 domain , microbiology and biotechnology , computational biology , receptor tyrosine kinase , cell signaling , phosphotyrosine binding domain , bioinformatics , philosophy , epistemology
Signal transduction pathways are typically controlled by regulated protein‐protein interactions, mediated by dedicated interaction domains. The prototype for such interactions involves the recognition of phosphotyrosine sites on receptor tyrosine kinases by the SH2 domains of cytoplasmic signaling proteins. Many other types of post‐translational modifications are also recognized by specific interaction domains, which therefore provide a general mechanism to couple the dynamic state of the proteome to cellular responses. There are ~100 classes of interaction domains present in human proteins, with each class being represented by up to 300 members. Interaction domains therefore represent a prevalent feature of the proteome. I will argue that they provide a simple mechanism for the evolution of new biological functions, and conversely that aberrant protein‐protein interactions are a common basis for disease. Adaptor proteins are composed exclusively of interaction sequences, and serve to couple signaling receptors to specific components of the core cellular machinery, thereby shaping the cellular response to a particular biological input. I will discuss the ability of adaptors to control cellular behaviour, and the mechanisms by which pathogenic proteins can exploit this molecular device to re‐wire cellular function.