[3] Protein kinase phosphorylation site sequences and consensus specificity motifs: Tabulations

ArticleinMethods in Enzymology 200:62-81 · February 1991with101 Reads
DOI: 10.1016/0076-6879(91)00127-I · Source: PubMed
Abstract
This chapter presents a table of phosphorylation site sequences for protein-serine/threonine and protein-tyrosine kinases. Over 240 phosphorylation site sequences along with the phosphorylated residue(s) are included in this table. The chapter presents another table containing consensus phosphorylation site motifs for each enzyme. The frequencies listed in this table are derived from the first table, unless indicated otherwise. The S : T ratio is for the total number of phosphorylation sites.
    • "In a recent study from our group comparing the mitochondrial phosphoproteomes of rat heart, liver, and skeletal muscle, the application of the Motif-X algorithm led to the identification of two motifs [K-X-X-X-pS] and [R-X-XpS] , which were enriched in mitochondrial phosphopeptides in all three tissues (Bak et al., 2013 ). These motifs have previously been reported to be recognized by PKA and PKC (Pearson and Kemp, 1991). In support of this finding, the PKC and PKA kinase families were also predicted as kinases for the largest fractions of mitochondrial phosphorylation sites, closely followed by the CKII and DNAPK kinase families (Bak et al., 2013 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Mitochondria are essential for several biological processes including energy metabolism and cell survival. Accordingly, impaired mitochondrial function is involved in a wide range of human pathologies including diabetes, cancer, cardiovascular, and neurodegenerative diseases. Within the past decade a growing body of evidence indicates that reversible phosphorylation plays an important role in the regulation of a variety of mitochondrial processes as well as tissue-specific mitochondrial functions in mammals. The rapidly increasing number of mitochondrial phosphorylation sites and phosphoproteins identified is largely ascribed to recent advances in phosphoproteomic technologies such as fractionation, phosphopeptide enrichment, and high-sensitivity mass spectrometry. However, the functional importance and the specific kinases and phosphatases involved have yet to be determined for the majority of these mitochondrial phosphorylation sites. This review summarizes the progress in establishing the mammalian mitochondrial phosphoproteome and the technical challenges encountered while characterizing it, with a particular focus on large-scale phosphoproteomic studies of mitochondria from human skeletal muscle.
    Article · Aug 2016
    • "Interestingly, the SNP changing R345 (arginine) to 345T (threonine) is located in close proximity to a frequently reported phosphorylation site (Munton et al, 2007; Trinidad et al, 2008; Huttlin et al, 2010; Wisniewski et al, 2010; Goswami et al, 2012). Therefore, we addressed the question to what extent the neighboring S (serine) at position 346 in humans and at position 347 in mouse is phosphorylated under wildtype conditions, and whether this phosphorylation is eventually altered due to the mutation of R to T, which alters typical phosphorylation motifs (Pearson & Kemp, 1991). Using quantitative mass spectrometry analysis and isotopically labeled peptides corresponding to the peptide containing S347, we detected that, although described as a potential activity-related phosphorylation site (Munton et al, 2007), S347 neighboring the SNP site showed only minor phosphorylation (4.73% of total PRG-1, Fig 1G). "
    [Show abstract] [Hide abstract] ABSTRACT: Loss of plasticity related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I)-balance in cortical networks. A recently reported SNP in prg-1 (R345T / mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1-function at the synapse due to its inability to control LPA levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1+/- mice, which are animal correlates of human PRG 1+/mut carriers, showed an altered cortical network function and behavioral changes indicative for psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG-recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of psychiatric diseases. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric disorders.
    Article · Nov 2015
    • "Interestingly, the SNP changing R345 (arginine) to 345T (threonine) is located in close proximity to a frequently reported phosphorylation site (Munton et al, 2007; Trinidad et al, 2008; Huttlin et al, 2010; Wisniewski et al, 2010; Goswami et al, 2012). Therefore, we addressed the question to what extent the neighboring S (serine) at position 346 in humans and at position 347 in mouse is phosphorylated under wildtype conditions, and whether this phosphorylation is eventually altered due to the mutation of R to T, which alters typical phosphorylation motifs (Pearson & Kemp, 1991). Using quantitative mass spectrometry analysis and isotopically labeled peptides corresponding to the peptide containing S347, we detected that, although described as a potential activity-related phosphorylation site (Munton et al, 2007), S347 neighboring the SNP site showed only minor phosphorylation (4.73% of total PRG-1, Fig 1G). "
    [Show abstract] [Hide abstract] ABSTRACT: Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases.
    Full-text · Article · Nov 2015
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