Date published: 2025-9-5

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Aftiphilin Activators

Aftiphilin's functional activity, predominantly within the domain of synaptic vesicle dynamics and neuronal transmission. Forskolin, for example, through the elevation of intracellular cAMP levels, indirectly promotes Aftiphilin's role by activating protein kinase A (PKA), which is known to phosphorylate substrates that could include Aftiphilin, thus enhancing vesicular trafficking. Similarly, compounds like 8-Bromo-cAMP and Dibutyryl-cAMP, as analogs of cAMP, permeate the cell membrane to activate PKA, which may lead to the phosphorylation of Aftiphilin or its interacting partners, thereby augmenting its function in synaptic vesicle endocytosis. Phosphatase inhibitors such as Calyculin A and Okadaic Acid increase the phosphorylation state of cellular proteins, which may include those associated with Aftiphilin, potentially enhancing its activity. Furthermore, PMA, as a PKC activator, could lead to the phosphorylation of proteins in the Aftiphilin pathway, indirectly boosting its role in membranefusion and trafficking.

The modulation of intracellular calcium levels plays a pivotal role in the activation of Aftiphilin, with Ionomycin increasing calcium concentrations, which may affect Aftiphilin's involvement in vesicle fusion processes. Likewise, Bay K8644, by stimulating L-type calcium channels, could amplify calcium-mediated signaling events that enhance Aftiphilin's function. The polyamine Spermine, which modulates ion channels, may also exert an influence on signaling pathways that activate Aftiphilin. In the realm of kinase regulation, Epigallocatechin Gallate (EGCG) inhibits various protein kinases, potentially shifting the balance of neuronal signaling pathways to favor Aftiphilin's activity. Anisomycin, although primarily a protein synthesis inhibitor, activates stress-activated protein kinases (SAPKs), which could signal through pathways that involve Aftiphilin, potentially increasing its activity related to stress responses in neurons. Lastly, Lithium Chloride's inhibition of GSK-3 may also indirectly enhance Aftiphilin's functional role in neurotransmitter release. Collectively, these activators exert nuanced and specific effects on the cellular signaling pathways, facilitating the enhancement of Aftiphilin's role in synaptic vesicle dynamics.

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