Protein kinase C (PKC) is a serine/threonine protein kinase, which plays a crucial role in signaling transduction mechanisms in many cell types and tissues. Gö 6983 is a pan-PKC inhibitor with IC50 values of 7nM, 7nM, 6nM, 10nM and 60nM (measure by protein kinase assay) for PKCα, PKCβ, PKCγ, PKCδ and PKCζ, whereas no activity against PKCμ with IC50 value of 20000nM. Gö 6983 is different with the normal pan-PKC inhibitor, such as staurosporine (IC50=40nM), for it has no effect on PKCμ, facilitating its ability to selective determination of PKCμ kinase activity in the presence of other PKC isoenzymes[1]. Treatment with Gö6983 induced the surface expression of NCRs, including NCR1, NCR2 and NCR3 (measured by relative MFI ratio) in a time- and dose-dependent manner, in primary NK cells. Pre-treatment with Gö6983 for 4h enhanced NK cell-mediated tumor cell killing at an E:T ratio of 3:1, performing as increased apoptosis and cytotoxicity on HepG2, Hep3B and HeLa cells, but has no cytotoxicity itself. Injection with 22.0ug of Gö6983 once daily on days-2, 0, 2, and 4 strongly inhibited tumor metastasis in pulmonary tumor metastasis models[2]. Inhibition of PKC through Gö 6983 could maintain ESC-specific epigenetic modifications at the chromatin domains of pluripotency genes and, thus maintain the expression of these genes in rat embryonic stem cells[3]. It was found that Gö6983 could also inhibit the activity of PfPKB, a protein kinase B homologue in Plasmodium falciparum[4].
作用机制
Gö 6983 acts at the ATP binding site which is highly conserved across PKC isoforms. [5]
Go 6983 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BT-474 cells
2 μM
Gö6983 completely blocked PMA-induced down-regulation of P-Rex1 protein expression and suppressed PMA inhibition of BT-474 cell growth.
Protein Cell. 2016 Jun;7(6):445-9.
MCF-7 cells
2 μM
Gö6983 completely blocked PMA-induced down-regulation of P-Rex1 protein expression and suppressed PMA inhibition of MCF-7 cell growth.
Protein Cell. 2016 Jun;7(6):445-9.
Primary mouse hepatocytes
10 μM
2 h
To investigate the protective effect of Go 6983 against APAP-induced cytotoxicity. Results showed that Go 6983 protected hepatocytes from APAP-induced necrosis through a JNK-independent pathway.
Hepatology. 2014 Apr;59(4):1543-1554.
HepG2 cells
10 μM
6 h
To investigate the effect of Go 6983 on MG132-induced LDLR transcription increase, it was found that Go 6983 completely abolished the increase in LDLR transcription induced by short-term treatment with MG132 (0-6 h).
Acta Pharmacol Sin. 2014 Aug;35(8):994-1004.
SH-SY5Y cells
1 μM
10 min
Go 6983 completely blocked CCh-induced MARCKS phosphorylation and reduced the stimulation of ERK1/2 phosphorylation by CCh, indicating that PKC plays an important role in the anti-apoptotic effect of CCh.
Br J Pharmacol. 2016 Oct;173(19):2910-28.
rat hippocampal CA1 region slices
10 µM
60 min
To investigate the effect of Go 6983 on DHPG-induced long-term depression (LTD), results showed that Go 6983 had no effect on basal synaptic transmission or DHPG-induced LTD.
Br J Pharmacol. 2001 Mar;132(5):1095-101.
rat hepatocytes
10 μM
1 hour
To investigate the effect of Go 6983 on the activity of PKCD/p38 and PKCD/JNK signaling pathways, the results showed that Go 6983 significantly inhibited the phosphorylation of PKCD, thereby inhibiting the phosphorylation of p38 and JNK.
Cell Prolif. 2018 Jun;51(3):e12437.
COS-7 cells
2.5 µM
1 hour
Go 6983 potently blocked rapid PKD catalytic activation in response to bombesin, but the inhibitory effect was significantly diminished at later times (45 min), indicating that PKD activation proceeds through early PKC-dependent and late PKC-independent mechanisms.
J Biol Chem. 2008 May 9;283(19):12877-87.
retinal venules
10 μM
30 min
To evaluate the role of PKC in ET-1-induced constriction of retinal venules, results showed that Go 6983 did not significantly affect basal tone or ET-1-induced constriction.
Diabetes. 2021 Oct;70(10):2353-2363.
Go 6983 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Long-Evans rats
Alcohol withdrawal model
Intra-LHb infusion
5 ng/200 nl/side
Single injection
Go-6983 alleviates anxiety- and depression-like behaviors associated with alcohol withdrawal by inhibiting PKC-γ and downregulating βCaMKII-AMPAR signaling
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