Table I.
Phosphorylation of different signaling pathways after Efavirenz treatment.
| BxPC-3 (pancreatic cancer cell line) | SBL-5 (primary fibroblasts) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Protein | Phosphory lation site | Overall | Ctrl. | EFV 10 min | EFV 1 h | EFV 24 h | Overall | Ctrl. | EFV 10 min | EFV 1 h | EFV 24 h | ||||||
| ERK1/2 | Thr202/Tyr204 | P<0.001 | 0.71 | 1,63 | (P<0.001) | 0.96 | (P=0.217) | 0.21 | (P=0.942) | P=0.077 | 2.72 | 4.17 | 3.55 | 1.91 | |||
| Akt | Ser473 | P<0.001 | 3.53 | 2.98 | (P=0.709) | 1.27 | (P=0.001) | 1.29 | (P=0.001) | P=0.042 | 1.64 | 1.97 | (P=0.929) | 3.24 | (P=0.035) | 2.40 | P=0.505 |
| Bad | Ser136 | P<0.001 | 2.87 | 3.52 | (P=0.056) | 2.32 | (P=0.113) | 2.40 | (P=0.205) | P=0.669 | 1.23 | 1.23 | 1.10 | 1.05 | |||
| HSP27 | Ser82 | P<0.001 | 0.44 | 0.53 | (P=0.056) | 0.36 | (P=0.141) | 0.03 | (P=0.003) | P=0.416 | 0.45 | 0.53 | 0.42 | 0.53 | |||
| Smad2 | Ser465/467 | P<0.001 | 0.87 | 0.72 | (P=0.264) | 0.67 | (P=0.075) | 0.40 | (P<0.001) | P=0.388 | 0.48 | 0.53 | 0.41 | 0.47 | |||
| p53 | Ser15 | P=0.110 | 0.14 | 0.18 | 0.18 | 0.09 | P=0.006 | 0.14 | 0.07 | (P=0.304) | 0.03 | (P=0.046) | 0.18 | (P=0.828) | |||
| p38 | Thr180/ | P<0.001 | 1.13 | 2.59 | (P<0.001) | 1.82 | (P=0.014) | 1.00 | (P=0.918) | P=0.007 | 0.78 | 1.29 | (P=0.137) | 1.56 | (P=0.012) | 0.85 | (P=0.987) |
| MAPK | Tyr182 | ||||||||||||||||
| SAPK/ | Thr183/ | P<0.001 | 0.75 | 0.77 | (P=0.989) | 0.57 | (P=0.066) | 0.45 | (P=0.001) | P=0.912 | 0.43 | 0.41 | 0.39 | 0.43 | |||
| JNK | Tyr185 | ||||||||||||||||
| PARP | Asp214a | P=0.216 | 0.61 | 0.66 | 1.18 | 1.35 | P=0.371 | 0.56 | 0.61 | 0.48 | 0.50 | ||||||
| Caspase-3 | Asp175a | P=0.854 | 0.41 | 0.38 | 0.44 | 0.41 | P=0.088 | 0.43 | 0.47 | 0.44 | 0.38 | ||||||
| Caspase-7 | Asp198a | P=0.002 | 0.48 | 0.40 | (P=0.286) | 0.36 | (P=0.073) | 0.28 | (P=0.001) | P=0.073 | 0.27 | 0.23 | 0.17 | 0.26 | |||
| IκBα | Total | P=0.001 | 9.03 | 8.07 | (P=0.629) | 6.51 | (P=0.024) | 5.40 | (P=0.001) | P=0.455 | 2.56 | 3.01 | 2.88 | 2.86 | |||
| Chk1 | Ser345 | P<0.001 | 0.99 | 0.92 | (P=0.954) | 1.38 | (P=0.072) | 0.52 | (P=0.021) | P=0.743 | 0.35 | 0.32 | 0.30 | 0.30 | |||
| Chk2 | Thr68 | P=0.432 | 0.83 | 0.77 | 0.86 | 0.74 | P=0.223 | 0.42 | 0.51 | 0.35 | 0.41 | ||||||
| IκBα | Ser32/36 | P<0.001 | 0.75 | 0.77 | (P=0.998) | 0.71 | (P=0.946) | 0.28 | (P=0.002) | P=0.686 | 0.22 | 0.25 | 0.19 | 0.25 | |||
| elF2α | Ser51 | P=0.726 | 0.76 | 0.71 | 0.76 | 0.66 | P=0.616 | 0.85 | 0.81 | 0.80 | 0.72 | ||||||
| TAK1 | Ser412 | P<0.001 | 15 | 14.84 | (P=0.714) | 13.84 | (P=0.107) | 8.69 | (P<0.001) | P=0.815 | 3.63 | 4.11 | 4.18 | 4.48 | |||
| Survivin | Total | P<0.001 | 1.34 | 1.13 | (P=0.142) | 0.98 | (P=0.004) | 0.35 | (P<0.001) | P=0.566 | 0.23 | 0.24 | 0.24 | 0.29 | |||
Changes of protein phosphorylation after Efavirenz 40 µmol/l treatment in the PathScan® Stress and Apoptosis Signaling Antibody Array.
Marks proteins that are cleaved and not phosphorylated. Statistical analysis was performed with ANOVA, overall P-values are shown. P<0.05 is indicated in bold. In case of statistical significance the Tukey's HSD test was used for post hoc analyses, these P-values are shown in brackets. ERK1/2, extracellular signal-related protein kinase; Akt, serine/threonine protein kinase B; Bad, B-cell lymphoma 2-associated death promotor; HSP27, heat shock protein 27; Smad2, mothers against decapentaplegic homolog 2; p53, tumor protein 53; p38 MAPK, p38, mitogen-activated protein kinase; SAPK/JNK, stress-activated protein kinase/c-Jun n-terminal kinase; PARP, poly [adenosine 5′-diphosphate-ribose] polymerase 1; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; Chk, checkpoint kinase; elF2α, E74-like factor 2 α; TAK1, TGF-β-activated kinase 1.