Date published: 2025-10-26

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COASTER Activators

Chemical activators of COASTER include a variety of compounds that can induce its activation through different cellular signaling pathways. Forskolin, known for its ability to increase cyclic AMP (cAMP) levels, directly stimulates the cAMP-dependent pathway, leading to the activation of protein kinase A (PKA). Activated PKA can phosphorylate COASTER, thereby increasing its activity. Similarly, Ionomycin, by elevating intracellular calcium levels, can activate calcium-dependent protein kinases which are capable of targeting COASTER for phosphorylation. Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), another kinase that can phosphorylate COASTER if it is within the substrate range of PKC. Epidermal Growth Factor (EGF) engages the EGF receptor and initiates a signaling cascade, culminating in the activation of kinases that can act on COASTER.

Additionally, Bradykinin, through its action on G-protein-coupled receptors, activates downstream kinases that can also target COASTER. Insulin, upon binding to its receptor, triggers the PI3K/AKT signaling pathway, which is known for its role in phosphorylating various substrates, including potentially COASTER. Anisomycin is a potent activator of the stress-activated protein kinases, including JNK, which may also lead to the phosphorylation of COASTER. Calyculin A and Okadaic Acid, as inhibitors of protein phosphatases, increase the phosphorylation state of proteins, which could result in the activation of COASTER by preventing its dephosphorylation. A23187, like Ionomycin, raises intracellular calcium and thus can activate kinases that phosphorylate COASTER. Bisindolylmaleimide I (BIM I), through its inhibitory action on PKC, can lead to the activation of alternative pathways that may result in COASTER activation. Lastly, Sphingosine-1-phosphate (S1P) binds to its specific G-protein-coupled receptors and could activate G-protein-coupled receptor kinases, which in turn may phosphorylate and activate COASTER, showcasing the intricate network of signaling pathways that can converge on the activation of this protein.

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