BIG3 Activators
Chemical activators of BIG3 can engage with the protein through various biochemical mechanisms, each instigating a unique aspect of BIG3's function in cellular processes. GTPγS, a non-hydrolyzable analog of GTP, binds to BIG3 and potentiates its activity as a guanine nucleotide exchange factor (GEF). This binding prevents the hydrolysis of GTP on ARF proteins, thus maintaining them in an active state which is essential for their role in vesicle trafficking. Similarly, Aluminum fluoride (AlF4-) functions by mimicking the phosphate group, facilitating the transition state in GDP to GTP exchange on ARF proteins, which is a critical step in the GEF activity of BIG3.
Forskolin and 8-Bromo-cAMP, by elevating intracellular cAMP levels, activate protein kinase A (PKA), which in turn can phosphorylate BIG3 or associated proteins, enhancing the GEF activity of BIG3. N6-Benzoyladenosine-3',5'-cyclic monophosphate (6-Bnz-cAMP) also acts as a PKA activator, fostering similar effects. In parallel, Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), which phosphorylates target proteins and may modulate BIG3's activity by altering its conformation or interaction with other proteins. Phosphatidylinositol 4,5-bisphosphate (PIP2) contributes to membrane dynamics, and fluctuations in its concentration can modulate BIG3 by influencing membrane curvature and GEF recruitment. The calcium ionophore Ionomycin raises intracellular calcium levels, which can then activate proteins that interact with BIG3, potentially enhancing its role in vesicle trafficking.
Moreover, the stabilization of actin filaments by Jasplakinolide can indirectly influence BIG3 activity by affecting the cytoskeletal dynamics that underpin vesicle formation and transport. Calyculin A and Okadaic Acid, by inhibiting protein phosphatases 1 and 2A, maintain proteins in a phosphorylated state, which could sustain the activation of BIG3. This mechanism ensures that BIG3 remains in an optimal conformation for interaction with ARF proteins and other molecules involved in vesicle trafficking. These chemical activators, through their diverse modes of action, converge on BIG3, modulating its GEF activity, and thereby influencing the ARF GTPase cycle critical for cellular trafficking processes.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Guanosine 5′-O-(3-thiotriphosphate) tetralithium salt | 94825-44-2 | sc-202639 | 10 mg | $456.00 | ||
GTPγS is a non-hydrolyzable analog of GTP. Binding of GTPγS to BIG3 would likely result in the activation of its guanine nucleotide exchange factor (GEF) activity, promoting the exchange of GDP for GTP on ARF proteins, which are small GTPases that BIG3 regulates. | ||||||
Forskolin | 66575-29-9 | sc-3562 sc-3562A sc-3562B sc-3562C sc-3562D | 5 mg 50 mg 1 g 2 g 5 g | $76.00 $150.00 $725.00 $1385.00 $2050.00 | 73 | |
Forskolin directly stimulates adenylate cyclase, increasing cAMP levels and activating PKA. PKA can phosphorylate proteins associated with vesicle trafficking, which may activate BIG3 by promoting its association with trafficking vesicles or other proteins in the ARF GTPase cycle. | ||||||
Ionomycin | 56092-82-1 | sc-3592 sc-3592A | 1 mg 5 mg | $76.00 $265.00 | 80 | |
Ionomycin is a calcium ionophore that increases intracellular calcium concentration, which can activate calcium-binding proteins. Since BIG3 is involved in vesicle trafficking, increased calcium may activate associated proteins that interact with BIG3, leading to its functional activation. | ||||||
PMA | 16561-29-8 | sc-3576 sc-3576A sc-3576B sc-3576C sc-3576D | 1 mg 5 mg 10 mg 25 mg 100 mg | $40.00 $129.00 $210.00 $490.00 $929.00 | 119 | |
PMA activates protein kinase C (PKC), which phosphorylates various target proteins. PKC-mediated phosphorylation could activate BIG3 by altering its conformation or interaction with other proteins, thereby enhancing its GEF activity. | ||||||
Calyculin A | 101932-71-2 | sc-24000 sc-24000A | 10 µg 100 µg | $160.00 $750.00 | 59 | |
Calyculin A is an inhibitor of protein phosphatases 1 and 2A. Inhibition of these phosphatases can result in increased phosphorylation levels of proteins, indirectly leading to the activation of BIG3 by maintaining it in a phosphorylated state. | ||||||
8-Bromo-cAMP | 76939-46-3 | sc-201564 sc-201564A | 10 mg 50 mg | $97.00 $224.00 | 30 | |
8-Bromo-cAMP is a cell-permeable cAMP analog that activates PKA. PKA may phosphorylate BIG3 or other proteins in the ARF GTPase cycle, leading to activation of BIG3's GEF activity. | ||||||
Okadaic Acid | 78111-17-8 | sc-3513 sc-3513A sc-3513B | 25 µg 100 µg 1 mg | $285.00 $520.00 $1300.00 | 78 | |
Okadaic Acid is a potent inhibitor of protein phosphatases 1 and 2A, leading to increased phosphorylation of proteins. This can result in the activation of BIG3 by preventing its dephosphorylation and maintaining its active state. | ||||||
Aluminum Fluoride | 7784-18-1 | sc-291881 sc-291881A | 10 g 50 g | $66.00 $245.00 | ||
Aluminum fluoride acts as an analog of the phosphate group and can activate G-proteins by stabilizing the transition state of GDP to GTP exchange. BIG3, as a GEF, may be functionally activated by AlF4- through the stabilization of the transition state during its catalytic action on ARF proteins. | ||||||
Jasplakinolide | 102396-24-7 | sc-202191 sc-202191A | 50 µg 100 µg | $180.00 $299.00 | 59 | |
Jasplakinolide stabilizes actin filaments and can lead to changes in cell morphology and motility. BIG3, being associated with vesicle trafficking, may be activated by alterations in actin dynamics, which could influence the recruitment or function of BIG3 in vesicle formation and transport. | ||||||