GKAP Inhibitors
Chemical inhibitors of GKAP function via diverse mechanisms to disrupt its activity within synaptic scaffolds, each targeting specific kinases that are responsible for phosphorylating GKAP or its associated proteins within the postsynaptic density (PSD). Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), which in turn phosphorylates GKAP, promoting its dissociation from the synaptic scaffolds and resulting in its functional inhibition. Conversely, Bisindolylmaleimide I and Staurosporine act as inhibitors of PKC, preventing the phosphorylation of GKAP. This ensures that GKAP remains associated with the synaptic scaffold, thereby maintaining its function within the PSD. H-89, operating as a protein kinase A (PKA) inhibitor, disrupts PKA-mediated phosphorylation pathways, which could otherwise lead to GKAP inhibition. Similarly, KN-93, Autocamtide-2-related inhibitory peptide (AIP), and K252a target Ca2+/calmodulin-dependent protein kinase II (CaMKII), a kinase implicated in phosphorylating synaptic proteins. By inhibiting CaMKII, these compounds help to maintain the structural integrity and function of GKAP within the PSD.
The phosphoinositide 3-kinase (PI3K) pathway, implicated in actin cytoskeleton dynamics, is another regulatory avenue for GKAP function. LY294002 and Wortmannin, both PI3K inhibitors, can stabilize the synaptic localization of GKAP by curtailing the dynamic reorganization of the actin cytoskeleton, thus preserving GKAP function. Moreover, U0126 and PD98059 are inhibitors of the MEK1/2 enzymes, which are upstream of extracellular signal-regulated kinases (ERK1/2) that phosphorylate synaptic proteins. These MEK inhibitors prevent the ERK-mediated phosphorylation cascade, which could lead to GKAP inhibition. Lastly, SB203580 targets the p38 MAPK pathway, a signaling route that can modify the phosphorylation state of proteins within the synapse. By inhibiting p38 MAPK, SB203580 can prevent alterations in synaptic protein interactions that would otherwise inhibit GKAP function, ensuring that GKAP continues to play its role in synaptic scaffolding.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
PMA | 16561-29-8 | sc-3576 sc-3576A sc-3576B sc-3576C sc-3576D | 1 mg 5 mg 10 mg 25 mg 100 mg | $41.00 $132.00 $214.00 $500.00 $948.00 | 119 | |
PMA activates protein kinase C (PKC), which can phosphorylate GKAP, leading to its functional inhibition by promoting its dissociation from synaptic scaffolds. | ||||||
Bisindolylmaleimide I (GF 109203X) | 133052-90-1 | sc-24003A sc-24003 | 1 mg 5 mg | $105.00 $242.00 | 36 | |
Bisindolylmaleimide I is a specific PKC inhibitor, which would prevent PKC-mediated phosphorylation of GKAP, thereby inhibiting GKAP's dissociation from the post-synaptic density (PSD). | ||||||
Staurosporine | 62996-74-1 | sc-3510 sc-3510A sc-3510B | 100 µg 1 mg 5 mg | $82.00 $153.00 $396.00 | 113 | |
Staurosporine inhibits a broad range of protein kinases including PKC. The inhibition of PKC can prevent the phosphorylation and subsequent functional inhibition of GKAP. | ||||||
KN-93 | 139298-40-1 | sc-202199 | 1 mg | $182.00 | 25 | |
KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII). As CaMKII phosphorylates proteins in the postsynaptic density, KN-93 can inhibit this phosphorylation, indirectly maintaining GKAP activity. | ||||||
K-252a | 99533-80-9 | sc-200517 sc-200517B sc-200517A | 100 µg 500 µg 1 mg | $129.00 $214.00 $498.00 | 19 | |
K252a is a kinase inhibitor known to inhibit CaMKII, among others. By inhibiting CaMKII, K252a can prevent the phosphorylation and subsequent functional inhibition of GKAP. | ||||||
LY 294002 | 154447-36-6 | sc-201426 sc-201426A | 5 mg 25 mg | $123.00 $400.00 | 148 | |
LY294002 is a PI3K inhibitor. PI3K signaling can regulate actin cytoskeleton dynamics, which is important for maintaining synaptic structures where GKAP is localized. Inhibition of PI3K can stabilize GKAP's synaptic localization and function. | ||||||
Wortmannin | 19545-26-7 | sc-3505 sc-3505A sc-3505B | 1 mg 5 mg 20 mg | $67.00 $223.00 $425.00 | 97 | |
Wortmannin is another PI3K inhibitor. Similar to LY294002, wortmannin can inhibit PI3K-related pathways and stabilize GKAP's position and function within the synaptic architecture. | ||||||
U-0126 | 109511-58-2 | sc-222395 sc-222395A | 1 mg 5 mg | $64.00 $246.00 | 136 | |
U0126 specifically inhibits MEK1/2, which is upstream of ERK1/2 kinase that can phosphorylate synaptic proteins. By inhibiting MEK, U0126 can prevent the phosphorylation cascade that may functionally inhibit GKAP. | ||||||
PD 98059 | 167869-21-8 | sc-3532 sc-3532A | 1 mg 5 mg | $40.00 $92.00 | 212 | |
PD98059 is a MEK inhibitor, which can prevent the activation of ERK and subsequent phosphorylation of synaptic proteins, thereby preventing the functional inhibition of GKAP. | ||||||
SB 203580 | 152121-47-6 | sc-3533 sc-3533A | 1 mg 5 mg | $90.00 $349.00 | 284 | |
SB203580 is a p38 MAPK inhibitor. The p38 MAPK pathway can influence the phosphorylation state of synaptic proteins and their interactions, thus, inhibition of p38 MAPK can prevent functional inhibition of GKAP. | ||||||