Phosphoproteomics: New insights into cellular signaling

Department of Pharmacology and the Alliance for Cellular Signaling, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
Genome biology (Impact Factor: 10.81). 02/2005; 6(9):230. DOI: 10.1186/gb-2005-6-9-230
Source: PubMed


Developments in the field of phosphoproteomics have been fueled by the need simultaneously to monitor many different phosphoproteins within the signaling networks that coordinate responses to changes in the cellular environment. This article presents a brief review of phosphoproteomics with an emphasis on the biological insights that have been derived so far.

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    • "However, these studies examined total proteins, and protein synthesis is a time-consuming process. In contrast, protein phosphorylation is a fast and reversible process that is involved in a wide variety of crucial cellular activities [6], in which the transcription and synthesis of new proteins are not involved. In all post-translational modification, phosphorylation and dephosphorylation is the most important which regulate all activites of life including cellular signal transduction, cell differentiation, cell growth and apoptosis [5-7]. "
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    ABSTRACT: Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia. Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia. Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness. These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.
    BMC Anesthesiology 01/2014; 14(1):3. DOI:10.1186/1471-2253-14-3 · 1.38 Impact Factor
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    • "Phosphoproteomics is used to study the phosphorylation of many proteins (the phosphoproteome), rather than individual proteins in a biological sample [13]. Bioinformatics uses computational algorisms to ascertain the physiologic impact of proteins at the systems level [14]. "
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    ABSTRACT: Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance.
    PLoS ONE 01/2014; 9(1):e83817. DOI:10.1371/journal.pone.0083817 · 3.23 Impact Factor
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    • "Phosphorylation suggests that the protein is in its active form (as is the case with several metabolic enzymes) and that upstream signals are active. Alternatively, phosphorylation could result in a conformational change that allows the modulation of specific activities [47]. "
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    PLoS ONE 07/2013; 8(6):e65433. DOI:10.1371/journal.pone.0065433 · 3.23 Impact Factor
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