Abstract:
:Protein kinases mediate much of the signal transduction in eukaryotic cells and defects in kinase function are associated with a variety of human diseases. To understand and correct these defects, we will need to identify the physiologically relevant substrates of these enzymes. The work presented here describes a novel approach to this identification process for the cAMP-dependent protein kinase (PKA) in Saccharomyces cerevisiae. This approach takes advantage of two catalytically inactive PKA variants, Tpk1K336A/H338A and Tpk1R324A, that exhibit a stable binding to their substrates. Most protein kinases, including the wild-type PKA, associate with substrates with a relatively low affinity. The binding observed here was specific to substrates and was dependent upon PKA residues known to be important for interactions with peptide substrates. The general utility of this approach was demonstrated by the ability to identify both previously described and novel PKA substrates in S. cerevisiae. Interestingly, the positions of the residues altered in these variants implicated a particular region within the PKA kinase domain, corresponding to subdomain XI, in the binding and/or release of protein substrates. Moreover, the high conservation of the residues altered and, in particular, the invariant nature of the R324 position suggest that this approach might be generally applicable to other protein kinases.
journal_name
Geneticsjournal_title
Geneticsauthors
Deminoff SJ,Howard SC,Hester A,Warner S,Herman PKdoi
10.1534/genetics.106.059238subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1909-17issue
4eissn
0016-6731issn
1943-2631pii
genetics.106.059238journal_volume
173pub_type
杂志文章相关文献
GENETICS文献大全abstract::During the first weeks of human immunodeficiency virus-1 (HIV-1) infection, cytotoxic T-lymphocytes (CTLs) select for multiple escape mutations in the infecting HIV population. In recent years, methods that use escape mutation data to estimate rates of HIV escape have been developed, thereby providing a quantitative f...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.113.150862
更新日期:2013-07-01 00:00:00
abstract::The replication of the rDNA complement of only one nucleolus organizer region during polytene chromosome formation (replicative dominance) was initially observed in Drosophila melanogaster. Here we demonstrate replicative dominance in Drosophila simulans and D. melanogaster/D. simulans interspecific hybrids. A second ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::The consequences of a discontinuity in the migration rate and of a geographical barrier in the habitat are studied in a diffusion model of migration and selection. The treatment is restricted to a single diallelic locus in a monoecious population in the absence of mutation and random drift. It is supposed further that...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::Four crosses were made between inbred Cannabis sativa plants with pure cannabidiol (CBD) and pure Delta-9-tetrahydrocannabinol (THC) chemotypes. All the plants belonging to the F(1)'s were analyzed by gas chromatography for cannabinoid composition and constantly found to have a mixed CBD-THC chemotype. Ten individual ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::Genic heterozygosity and variation were studied in the permanent translocation heterozygotes Oenothera biennis I, Oe. biennis II, Oe. biennis III, Oe. strigosa, Oe. parviflora I, Oe. parviflora II, and in the related bivalent formers Oe. argillicola and Oe. hookeri. From variation at 20 enzyme loci, we find that trans...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1975-03-01 00:00:00
abstract::Inbreeding depression, which refers to reduced fitness among offspring of related parents, has traditionally been studied using pedigrees. In practice, pedigree information is difficult to obtain, potentially unreliable, and rarely assessed for inbreeding arising from common ancestors who lived more than a few generat...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.130922
更新日期:2011-09-01 00:00:00
abstract::The behavior of chromosomal inversions in Escherichia coli depends upon the region they affect. Regions flanking the replication terminus have been termed nondivisible zones (NDZ) because inversions ending in the region were either deleterious or not feasible. This regional phenomenon is further analyzed here. Thirty ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::We have shown that the phenotypes resulting from hypomorphic mutations (causing reduction but not complete loss of function) in two X-linked genes can be used as a genetic assay for X-chromosome dosage compensation in Caenorhabditis elegans between males (XO) and hermaphrodites (XX). In addition we show that recessive...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::The contribution of epigenetic alterations to natural variation for gene transcription levels remains unclear. In this study, we investigated the functional targets of the maize chromomethylase ZMET2 in multiple inbred lines to determine whether epigenetic changes conditioned by this chromomethylase are conserved or v...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.107.072702
更新日期:2007-10-01 00:00:00
abstract::One crossover point between a pair of homologous chromosomes in meiosis appears to interfere with occurrence of another in the neighborhood. It has been revealed that Drosophila and Neurospora, in spite of their large difference in the frequency of crossover points, show very similar plots of coincidence-a measure of ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract::The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased e...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::The eukaryotic cytoplasm contains a variety of ribonucleoprotein (RNP) granules in addition to the better-understood membrane-bound organelles. These granules form in response to specific stress conditions and contain a number of signaling molecules important for the control of cell growth and survival. However, relat...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.116.187419
更新日期:2016-07-01 00:00:00
abstract::We have studied how a set of male-specific sensory neurons in Caenorhabditis elegans establish axonal connections during postembryonic development. In the adult male, 9 bilateral pairs of ray sensory neurons innervate an acellular fan that serves as a presumptive tactile and olfactory organ during copulation. We visua...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.057000
更新日期:2006-07-01 00:00:00
abstract::The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified i...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.112.140152
更新日期:2012-08-01 00:00:00
abstract::A BC1 population of the self-compatible tomato Lycopersicon esculentum and its wild self-incompatible relative L. hirsutum f. typicum was used for restriction fragment length polymorphism linkage analysis and quantitative trait loci (QTL) mapping of reproductive behavior and floral traits. The self-incompatibility loc...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Multilocus surveys of sequence variation can be used to identify targets of directional selection, which are expected to have reduced levels of variation. Following a population bottleneck, the signal of directional selection may be hard to detect because many loci may have low variation by chance and the frequency sp...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.054312
更新日期:2006-06-01 00:00:00
abstract::A genetic map for the model legume Lotus japonicus has been developed. The F(2) mapping population was established from an interspecific cross between L. japonicus and L. filicaulis. A high level of DNA polymorphism between these parents was the source of markers for linkage analysis and the map is based on a framewor...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::Estimating the fixation probability of a beneficial mutation has a rich history in theoretical population genetics. Typically, to attain mathematical tractability, we assume that generation times are fixed, while the number of offspring per individual is stochastic. However, fixation probabilities are extremely sensit...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.107.072009
更新日期:2007-07-01 00:00:00
abstract::BTB-zinc finger transcription factors play many important roles in metazoan development. In these proteins, the BTB domain is critical for dimerization and for recruiting cofactors to target genes. Identification of these cofactors is important for understanding how BTB-zinc finger proteins influence transcription. He...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.109.111591
更新日期:2010-04-01 00:00:00
abstract::We have initiated an analysis of protein kinase A (PKA) in Drosophila using transgenic techniques to modulate PKA activity in specific tissues during development. We have constructed GAL4/UAS-regulated transgenes in active and mutant forms that encode PKAc, the catalytic subunit of PKA, and PKI(1-31), a competitive in...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::The linkage disequilibrium pattern analysis is a method that allows one to detect present and past events of selection. We applied it to our data on the inversions of Drosophila mediopunctata and to published data of Drosophila subobscura, which are systems probably under complex modes of selection. The method gave me...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::The I factor (IF) is a LINE-like transposable element from Drosophila melanogaster. IF is silenced in most strains, but under special circumstances its transposition can be induced and correlates with the appearance of a syndrome of female sterility called hybrid dysgenesis. To elucidate the relationship between IF ex...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::DNA topoisomerases, enzymes that alter the superhelicity of DNA, have been implicated in such critical cellular functions as transcription, DNA replication, and recombination. In the yeast Saccharomyces cerevisiae, a null mutation in the gene encoding topoisomerase I (TOP1) causes elevated levels of mitotic recombinat...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::An analysis of the effects of spontaneous mutations affecting age-specific mortality was conducted using 29 lines of Drosophila melanogaster that had accumulated spontaneous mutations for 19 generations. Divergence among the lines was used to estimate the mutational variance for weekly mortality rates and the covarian...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Double-strand DNA breaks can be repaired by any of several alternative mechanisms that differ greatly in the nature of the final repaired products. We used a reporter construct, designated "Repair reporter 3" (Rr3), to measure the relative usage of these pathways in Drosophila germ cells. The method works by creating ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.050138
更新日期:2006-02-01 00:00:00
abstract::Dravet syndrome is a developmental epileptic encephalopathy caused by pathogenic variation in SCN1A To characterize the pathogenic substitution (p.H939R) of a local individual with Dravet syndrome, fibroblast cells from the individual were reprogrammed to pluripotent stem cells and differentiated into neurons. Sodium ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.120.303399
更新日期:2020-08-01 00:00:00
abstract::The transcription factors WHITE COLLAR-1 (WC-1) and WHITE COLLAR-2 (WC-2) interact to form a heterodimeric complex (WCC) that is essential for most of the light-mediated processes in Neurospora crassa. WCC also plays a distinct non-light-related role as the transcriptional activator in the FREQUENCY (FRQ)/WCC feedback...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Despite remarkable success in uncovering many risk variants and providing novel insights into disease biology, genetic variants identified to date fail to explain the vast majority of the heri...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.115.185009
更新日期:2016-03-01 00:00:00
abstract::The three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remain debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization an...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.119.302978
更新日期:2020-03-01 00:00:00
abstract::A sample of 16 Minutes, representing 12 loci distributed over all the chromosome arms and including 3 pairs of alleles and 4 deficiencies, has been studied with respect to several developmental and recombinational parameters. Cell marker mutants located in most of the chromosome arms were used to assess (1) spontaneou...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1975-04-01 00:00:00