Date published: 2025-9-14

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9330101J02Rik Activators

Chemical activators of cilia and flagella associated protein 46 can engage various signaling pathways to initiate its functional activation. Forskolin, for instance, is known for its ability to directly stimulate adenylate cyclase, thereby increasing intracellular cAMP levels. This elevation in cAMP can lead to the activation of protein kinase A (PKA), which may then phosphorylate cilia and flagella associated protein 46, enhancing its activity. Similarly, IBMX functions to inhibit phosphodiesterases, which break down cAMP, thus sustaining its levels within the cell and indirectly supporting the activation of PKA that can phosphorylate cilia and flagella associated protein 46. Another activator, Phorbol 12-myristate 13-acetate (PMA), targets protein kinase C (PKC), which is a kinase known to phosphorylate a vast array of proteins. Upon activation, PKC may target cilia and flagella associated protein 46, leading to its activation through direct phosphorylation.

In addition to these, ionomycin and A23187 exert their effects by increasing intracellular calcium concentrations, which can activate a range of calcium-dependent kinases. These kinases, in turn, have the potential to phosphorylate and activate cilia and flagella associated protein 46. Thapsigargin operates by inhibiting the SERCA pump, leading to a similar increase in intracellular calcium that could trigger the activation of cilia and flagella associated protein 46 through calcium-responsive elements. Phosphatase inhibitors such as okadaic acid and calyculin A prevent the dephosphorylation of proteins, thereby maintaining cilia and flagella associated protein 46 in a phosphorylated, and thus active state. Anisomycin activates stress-activated protein kinases, which may target cilia and flagella associated protein 46 for phosphorylation and consequent activation. The lipid molecule phosphatidic acid can initiate the mTOR signaling cascade, which includes kinases capable of phosphorylating cilia and flagella associated protein 46, whereas oleoylethanolamide activates PPAR receptors that might stimulate kinases to phosphorylate and activate this protein. Lastly, sphingosine-1-phosphate, through its G-protein-coupled receptors, can activate downstream kinases which are potential activators of cilia and flagella associated protein 46 through phosphorylation events.

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