Application of High-Throughput Assays to Examine Phospho-Modulation of the Late Steps of Regulated Exocytosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Isolation of Cortical Vesicles and Drug Treatments
2.3. High-Throughput Methodology
3. Results
3.1. Effects of Protein Kinase Inhibitors
3.2. Effects of Phosphatase Inhibitors
3.3. Effects of Inhibiting Lipid Kinases
4. Discussion
4.1. Protein Kinase C, Protein Kinase A, Calmodulin-dependent Protein Kinase II
4.2. Rho Kinase
4.3. Casein Kinase 2
4.4. Dephosphorylation
4.5. Lipid Phosphorylation
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Compound | Molecular Target | Dose Used | Refs |
---|---|---|---|
Phorbol 12-myristate 13-acetate (PMA) | PKC activator | 100 nM | [12,14,37,38,39,40] |
Gö 6983 | PKC inhibitor | 10 µM | [41,42,43,44,45,46] |
PKC inhibitory peptide (19–36; RFARKGALRQKNVHEVKN) | PKC inhibitor | 10 µM | [13,47,48] |
Staurosporine | Broad spectrum kinase inhibitor | 4 µM | [49,50,51,52,53,54,55,56,57,58] |
α-naphthyl phosphate (α-NP) | Broad spectrum phosphatase inhibitor | 5 mM | [14] |
Okadaic acid | Dual protein phosphatase 1/2A inhibitor | 1 µM | [12,20,28,59,60,61,62] |
Calcineurin (CaN) inhibitory peptide (457–482; ITSFEEAKGLDRINERMPPRRDAMP) | CaN inhibitor | 100 µM | [20,63] |
PKA inhibitory peptide (6–22; TYADFIASGRTGRRNAI) | Protein kinase A inhibitor | 1 µM | [64,65,66] |
4,5,6,7-tetrabromobenzotriazole (TBB) | Casein kinase 2 (Ck2) inhibitor | 25 µM | [67,68] |
GSK 429286 | Rho kinase (ROCK) inhibitor | 2 µM | [69,70,71,72] |
Bosutinib | Dual abl/src kinase inhibitor | 10 µM | [73,74,75,76] |
A419259 | Src kinase inhibitor | 500 nM | [77,78,79,80,81] |
Autocamtide-2-related inhibitory peptide (AIP) (KKALRRQEAVDAL) | Calmodulin-dependent protein kinase II (CaMK II) inhibitor | 10 µM | [82,83] |
STO609 | Ca2+/calmodulin-dependent protein kinase kinase (CaMK kinase) inhibitor | 25 µM | [84,85,86,87] |
R59022 | Diacylglycerol kinase inhibitor | 12.5 µM | [88,89] |
NVP231 | Ceramide kinase inhibitor | 100 nM | [90,91,92,93] |
Dimethylsphingosine (DMS) | Sphingosine kinase inhibitor | 100 µM | [94] |
Enzyme Name | Percent Identity | Percent Similarity |
---|---|---|
Protein kinase C | 68.4 | 80 |
PKC conserved region 1 (phorbol ester binding site) | 90 | 92 |
Serine/threonine catalytic domain | 81.1 | 92.7 |
cAMP-dependent protein kinase catalytic subunit αisoform | 78.7 | 89.8 |
Casein kinase 2 α subunit | 79.1 | 86.9 |
Abl-related protein tyrosine kinase | 69.1 | 80.6 |
Src-family protein tyrosine kinase | 54.4 | 67.9 |
Rho kinase | 47.2 | 64.4 |
Rho kinase associated coiled coil (containing PH domain) | 55.4 | 69.6 |
Calmodulin-dependent protein kinase 1 | 57.6 | 76.6 |
Calmodulin-dependent protein kinase kinase | 33.4 | 44.3 |
Protein phosphatase 2A catalytic subunit | 94.4 | 97.4 |
Calcineurin B homologous protein | 62.2 | 74.0 |
Diacylglycerol kinase | 52.8 | 65.8 |
Ceramide kinase | 44.8 | 66.5 |
Sphingosine kinase | 43.3 | 61.0 |
Sphingosine kinase conserved domains: | ||
C 1 | 64.7 | 76.5 |
C 2 | 40.0 | 72.0 |
C 3 | 75.0 | 91.7 |
C 4 | 57.1 | 82.1 |
C 5 | 80.0 | 100.0 |
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Abbineni, P.S.; Coorssen, J.R. Application of High-Throughput Assays to Examine Phospho-Modulation of the Late Steps of Regulated Exocytosis. High-Throughput 2017, 6, 17. https://doi.org/10.3390/ht6040017
Abbineni PS, Coorssen JR. Application of High-Throughput Assays to Examine Phospho-Modulation of the Late Steps of Regulated Exocytosis. High-Throughput. 2017; 6(4):17. https://doi.org/10.3390/ht6040017
Chicago/Turabian StyleAbbineni, Prabhodh S., and Jens R. Coorssen. 2017. "Application of High-Throughput Assays to Examine Phospho-Modulation of the Late Steps of Regulated Exocytosis" High-Throughput 6, no. 4: 17. https://doi.org/10.3390/ht6040017