Chemical activators of Olr251 can engage various intracellular signaling cascades that converge on this protein to modulate its activity. Phorbol 12-myristate 13-acetate (PMA) and Phosphatidylserine are both activators of protein kinase C (PKC), which can phosphorylate Olr251, leading to its functional activation. Forskolin acts by increasing cellular cAMP levels, which activates protein kinase A (PKA). PKA can then phosphorylate Olr251, resulting in its activation. Similarly, Ionomycin raises intracellular calcium levels, which can activate calcium/calmodulin-dependent protein kinases, potential activators of Olr251 through phosphorylation. BAY K8644 and FPL 64176 both stimulate L-type calcium channels, thus raising intracellular calcium concentrations and promoting activation of Olr251 through calcium-sensitive kinases.
Additionally, Anisomycin activates stress-activated protein kinases that can phosphorylate Olr251, leading to its activation. Calyculin A and Okadaic Acid both inhibit protein phosphatases, which would otherwise dephosphorylate Olr251, thereby maintaining Olr251 in an active state. Cyclopiazonic Acid, by inhibiting calcium ATPase, disrupts calcium homeostasis, which can lead to the activation of Olr251 through the action of downstream kinases. Picrotoxin, through its modulation of GABA receptors, can lead to neuronal excitation and subsequent activation of kinases that can phosphorylate and activate Olr251. Ryanodine interacts with ryanodine receptors affecting calcium release from intracellular stores, which may result in the activation of intracellular kinases that phosphorylate and activate Olr251, further illustrating the diverse mechanisms through which chemical activators can initiate the activation of this protein.
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