Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2.
Kinases regulate key signaling processes that are increasingly implicated in development and disease. Kinase modulators have become important therapeutic tools and often target catalytic domains that are among the most structurally and functionally conserved regions of these enzymes. Such therapies lose efficacy as mutations conferring resistance arise. Because interactions between distinct and often distant regions of kinases can be critical, we took an unbiased genetic approach to identify sites within the protein kinase A homolog Tpk2 that contribute to its biological activity. Because many of these map outside the conserved core, this approach should be broadly useful in identifying new, more kinase-specific therapeutic targets.
Kennedy
Eileen J
EJ
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0375, USA.
Ghosh
Gourisankar
G
Pillus
Lorraine
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D016384:Consensus Sequence; D017868:Cyclic AMP-Dependent Protein Kinases; D017931:DNA Primers; D005822:Genetic Vectors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C457179:TPK2 protein, S cerevisiae