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A chemical genetic approach to understand inositol polyphosphate signaling (794.6)
Author(s) -
Dul Barbara,
Bratz Jeffrey,
Fiedler Dorothea
Publication year - 2014
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.28.1_supplement.794.6
Subject(s) - inositol , yeast , second messenger system , signal transduction , biology , chemical genetics , kinase , genetic screen , saccharomyces cerevisiae , function (biology) , microbiology and biotechnology , polyphosphate , cell signaling , protein kinase a , biochemistry , genetics , phenotype , receptor , gene , small molecule , phosphate
Cells regulate their growth in response to nutritional and mitogenic signals through signaling pathways that are well defined and tightly controlled by second messengers. It is critical that these messengers respond quickly and balance cellular responses. Inositol polyphosphates (IPs) have been found to play an important role in signaling and highly conserved from yeast to higher organisms. Genetic studies in yeast ascribe important functions for IPs in many cellular processes, including telomere maintenance and nutrient sensing. IP deficient mice exhibit several defects in insulin secretion and are resistant to age and diet induced obesity. We are interested in understanding the mechanisms by which the various IPs function within cells and have begun to study this pathway with a chemical genetic approach. This approach relies on designing orthogonal protein/ligand pairs ‐ by introducing a mutation in the kinase active site and using a size complementary ATP analog ‐ and has successfully been applied to numerous protein kinases. We found that this approach works with yeast inositol kinases Arg82, Ipk1, and Kcs1. Because yeast screens remain the most versatile tool for assessing functional genomic interactions at an organismal level, we exploit the yeast system to investigate IP signaling in transcriptional regulation. We anticipate that a number of these fundamental signaling roles will be maintained in higher organisms. Grant Funding Source : NIH