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Modulation of Signaling Proteins by Reversible Cysteine Modification
Author(s) -
Keyes Jeremiah David,
Nelson Kimberly,
Parsonage Derek,
Daniel Larry,
Furdui Cristina,
Poole Leslie
Publication year - 2013
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.27.1_supplement.993.3
Subject(s) - signal transduction , second messenger system , microbiology and biotechnology , kinase , protein kinase a , lysophosphatidic acid , cell signaling , chemistry , lipid signaling , protein kinase c , signal transducing adaptor protein , phosphatase , biochemistry , biology , phosphorylation , enzyme , receptor
In order to elicit an appropriate response toward a stimulus, cells have developed intricate systems to control signaling pathways. These pathways are often centered on kinase cascades, which are modulated by 2 nd messengers and protein‐protein interactions. Such modulation is necessary for the spatial‐temporal control of kinase signal exertion. It is through these mechanisms that a signal can induce a specific response through a core kinase cascade that is shared by other signals to elicit different responses. Recently recognized 2 nd messengers are Reactive Oxygen Species (ROS) such as H 2 O 2 . These ROS oxidize cysteine residues of proteins, which has the potential to modify the surface and configuration of a protein, thereby affecting interactions with small molecules, proteins, lipids, or nucleotides. Our collaborative team recently identified that ROS are necessary for the survival and proliferative response of ovarian and prostate cancer cells to lysophosphatidic acid (LPA), a signaling lipid found in the ascites fluid of ovarian and prostate tumors. Using techniques developed by our collaborative team, I have found that key kinases and phosphatases are oxidized during LPA signaling. Additionally, I report signaling proteins that are reversibly inhibited by oxidation towards specific substrates as a result of LPA signaling.