文章基本信息

标题：Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase
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作者：Angela P. Won ; Joan E. Garbarino ; Wendell A. Lim 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：24
页码：9809-9814
DOI：10.1073/pnas.1016337108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The yeast Saccharomyces cerevisae has four distinct mitogen-activated protein kinase kinases (MAPKKs), each of which has a distinct functional identity characterized by communication with specific upstream and downstream partners to form distinct functional pathways. These four kinases belong to one family, sharing closely related catalytic domains. How have these four related kinases diverged to take on four distinct functional roles? The specificity of an enzyme for a particular substrate is often thought to reside in differences in the catalytic domain. However, many kinases, including MAPKKs, have modular interaction domains and motifs that have been shown to play an important role in determining the specificity of kinases through recruitment to specific partners and complexes. Here we probe the relative importance of catalytic domain interactions versus recruitment interactions in defining the functional identity of MAPKKs by asking whether we can use recruitment interactions to force other MAPKK catalytic domains to play the functional role of the mating MAPKK, Ste7. We find that two alternative MAPKKs, Pbs2 and Mkk2, can be forced to functionally replace the mating MAPKK Ste7, but only if the proper set of recruitment interactions are grafted onto their catalytic domains. These results show that within a family of kinases, recruitment interactions can play a dominant role in defining functional identity, and is consistent with a model in which new kinase functions can arise through recombination of existing catalytic domains with new interaction modules.
关键词：protein interactions ; signal transduction ; evolution ; synthetic biology