Chemical activators of C2orf18 can be involved in various intracellular signaling pathways, leading to its functional activation. Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), which is a kinase known to phosphorylate a variety of proteins. When PKC is activated by PMA, it can directly phosphorylate C2orf18, resulting in its activation. Similarly, Ionomycin, by increasing intracellular calcium levels, can activate calcium-dependent kinases that also have the capability to phosphorylate and hence activate C2orf18. Forskolin, through the activation of adenylate cyclase, raises the levels of cAMP within the cell, which then activates PKA. PKA, being another kinase, can subsequently phosphorylate C2orf18 to activate it. Inhibition of protein phosphatases by Calyculin A and Okadaic Acid leads to a net increase in phosphorylation levels of cellular proteins since these compounds prevent the dephosphorylation of proteins like C2orf18, maintaining it in an active state.
Additionally, Anisomycin, by activating stress-activated protein kinases, can lead to the phosphorylation and consequent activation of C2orf18. Thapsigargin's inhibition of the SERCA pump elevates cytosolic calcium, which again can result in the activation of C2orf18 via calcium-dependent kinases. The phosphorylated form of FTY720 modulates sphingosine-1-phosphate receptor signaling, which can initiate a cascade of kinase activations resulting in the phosphorylation and activation of C2orf18. Zinc Pyrithione's activation of the MAPK pathway can also lead to the phosphorylation and activation of C2orf18. The role of reactive oxygen species such as Hydrogen Peroxide is not to be underestimated, as it can activate intracellular kinases in response to oxidative stress, which can then phosphorylate C2orf18, leading to its activation. S-Nitroso-N-acetylpenicillamine (SNAP) releases nitric oxide, which activates guanylyl cyclase, raising cGMP levels and activating PKG, a kinase that can phosphorylate and activate C2orf18. Lastly, Brefeldin A disrupts the Golgi apparatus function, inducing a stress response that can activate kinases capable of phosphorylating and activating C2orf18.
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