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Chemical activators of JAKMIP3 employ diverse cellular mechanisms to initiate its activation. Staurosporine, a broad-spectrum protein kinase inhibitor, indirectly activates JAKMIP3 by inhibiting a kinase responsible for JAKMIP3's inactivity, thus resulting in an increase in JAKMIP3 activity. Prostaglandin E2 operates through its receptor to raise intracellular cAMP levels, activating protein kinase A (PKA), which can subsequently phosphorylate and activate JAKMIP3. Similarly, Forskolin, by elevating cAMP, indirectly activates PKA, leading to the activation of JAKMIP3. Epidermal Growth Factor (EGF) binds to its specific receptor, triggering the PI3K/AKT pathway, which can lead to JAKMIP3 activation through subsequent phosphorylation events. Phorbol 12-myristate 13-acetate (PMA) engages protein kinase C (PKC), which is known to phosphorylate and activate JAKMIP3 as part of its signaling cascade.

Ionomycin increases intracellular calcium, activating calmodulin-dependent kinases that can phosphorylate JAKMIP3. Thapsigargin raises cytosolic calcium levels by inhibiting SERCA, which leads to the activation of calcium-dependent kinases capable of activating JAKMIP3. Okadaic Acid and Calyculin A inhibit protein phosphatase 2A, resulting in increased phosphorylation levels of proteins, including JAKMIP3. Anisomycin activates the JNK and p38 MAP kinase pathways, leading to JAKMIP3 activation. Phosphatidic Acid acts as a second messenger to activate mTOR and PKC pathways, which can result in JAKMIP3 activation. Lastly, PF-4708671 selectively inhibits p70 S6 kinase, which can lead to the compensatory activation of other kinases or pathways that activate JAKMIP3, showcasing the intricate network of cellular signaling that converges on the regulation of this particular protein.