Chemical activators of Trav14n-1 utilize various cellular signaling pathways to modulate the activity of this protein. Phorbol 12-myristate 13-acetate (PMA) is a potent activator of protein kinase C (PKC), which directly phosphorylates Trav14n-1, leading to its activation. A similar mechanism is employed by Diacylglycerol (DAG) and Oleic Acid, both of which also activate PKC, subsequently influencing the phosphorylation status of Trav14n-1. Forskolin works through a different pathway, raising intracellular cAMP levels, which in turn activate protein kinase A (PKA). PKA then phosphorylates and activates Trav14n-1. Additionally, Epidermal Growth Factor (EGF) binds to its receptor to initiate a cascade of events through the MAPK/ERK pathway, culminating in the phosphorylation and activation of Trav14n-1.
Calcium plays a pivotal role in the activation of Trav14n-1 through several agents that alter intracellular calcium levels. Ionomycin facilitates the influx of calcium, while Thapsigargin inhibits the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA), both leading to increased intracellular calcium concentrations which activate calcium-dependent protein kinases that phosphorylate Trav14n-1. Calyculin A and Okadaic Acid contribute to the phosphorylation state of Trav14n-1 by inhibiting protein phosphatases 1 and 2A, which would otherwise dephosphorylate and inactivate Trav14n-1. Furthermore, Phosphatidic Acid activates the mTOR signaling pathways, which are known to phosphorylate a broad array of proteins, potentially including Trav14n-1. Anisomycin, though primarily known as a protein synthesis inhibitor, activates stress-activated protein kinases like JNK, which may also target and phosphorylate Trav14n-1. Lastly, Hydrogen Peroxide, a reactive oxygen species, can activate various kinases such as PKC, contributing to the phosphorylation landscape of Trav14n-1.
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