Sequence patches on MAPK surfaces define protein-protein interactions 英文参考文献.docVIP

Minireview Sequence patches on MAPK surfaces define protein-protein interactions Gary L Johnson* and Shawn M Gomez? Addresses: *Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7365, USA. ?Joint Department of Biomedical Engineering, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7365, USA. Correspondence: Gary L Johnson. E-mail: glj@ Published: 5 June 2009 Genome Biology 2009, 10:222 (doi:10.1186/gb-2009-10-6-222) The electronic version of this article is the complete one and can be found online at /2009/10/6/222 ? 2009 BioMed Central Ltd Abstract Recent studies on the modularity of mitogen-activated protein kinases show how redesigning ‘surface patches’ on a protein can change the topology of a signaling network. In cells, protein-protein interaction domains control the organization of multiprotein complexes in signal trans- duction networks, thereby determining the responses of cells to many different stimuli [1]. Such domains are generally defined as independently folded structural modules that can bind a protein ligand or a peptide motif. There are at least 81 defined protein-interaction domains in eukaryotic cells that control the organization and responses of signaling networks [2]. Even a given domain can have significant complexity and be used repeatedly in different contexts. For example, more than 120 Src-homology 2 (SH2) domains - which recognize phospho-tyrosines - are encoded in the human genome. Each SH2 domain has amino acid variations that alter the sequence context within which it recognizes a phospho-tyrosine residue. In higher eukaryotes especially, a single protein is typically composed of multiple domains, and so the ability to reconfigure the repertoire of domain composition and position within a protein provides