Date published: 2025-10-14

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Rab11-FIP2 Activators

Rab11-FIP2 activators encompass a spectrum of chemical compounds that indirectly enhance the functional activity of Rab11-FIP2, primarily through the modulation of cellular signaling pathways that intersect with Rab11-FIP2's role in vesicle trafficking. Forskolin, which elevates cAMP, and 8-Bromo-cAMP, a cAMP analog, both augment PKA activity, leading to subsequent phosphorylation of proteins that synergize with Rab11-FIP2, thus promoting its role in directing vesicle trafficking and recycling. Phorbol 12-myristate 13-acetate (PMA) and Ionomycin activate PKC and calcium-dependent kinases, respectively, which can also phosphorylate and alter the activity of proteins interacting with Rab11-FIP2, enhancing its endocytic recycling capabilities. Compounds such as Epigallocatechin gallate (EGCG) and Okadaic Acid manipulate kinase activity by either inhibiting certain kinases or inhibiting phosphatases like PP1 and PP2A, resulting in a favorable phosphorylation environment for Rab11-FIP2's function in membrane trafficking.

In addition, LY294002 and Wortmannin, by inhibiting PI3K, alter AKT signaling cascades that are crucial for vesicle formation and trafficking, indirectly facilitating Rab11-FIP2's activity. Sphingosine-1-phosphate, through its receptor-mediated signaling, influences cytoskeletal dynamics crucial for Rab11-FIP2's role in vesicle movement and docking. Calyculin A, sharing a mechanism similar to Okadaic Acid, promotes hyperphosphorylation that could enhance Rab11-FIP2's involvement in vesicular transport. Moreover, Adenosine 5'-triphosphate (ATP) provides the phosphate groups for kinase-mediated phosphorylation, which is fundamental for the regulation of Rab11-FIP2 activity. Lastly, Thapsigargin's role in increasing cytosolic calcium levels indirectly supports the activation of calcium-dependent signaling pathways, which are essential for Rab11-FIP2-mediated endosomal functions.

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