The role of epidermal growth factor and cholinergic receptor agonists and antagonists in MAPK signal transduction in K562 cells
Year 2024,
, 86 - 91, 28.01.2024
Selda Güler Atmaca
,
Banu Aydın
,
Hulya Cabadak
Abstract
Objective: Muscarinic receptors (M1-M5) are members of the G protein-coupled receptor superfamily and are effective in physiological
functions through G proteins. Recent studies suggested that cholinergic receptors mediate cellular activities in hematopoietic cells.
The aim of this study was to investigate the potential role of mitogen-activated protein kinases (MAPK) signaling extracellular signalregulated
kinases 1 and 2 (ERK1/2)/phosphorylated ERK1/ (pERK1/2) pathways in chronic myeloid leukemia (K562) cells.
Materials and Methods: Chronic myeloid leukemia cells were cultured. Cells were incubated in the presence of muscarinic receptor
agonist, antagonist and epidermal growth factor (EGF). To detect MAPK activation, ERK/pERK protein expression levels were
determined by western blot method techniques.
Results: Our study results showed that cholinergic agents and EGFs affect the MAPK pathway in the human K562 cell line.
Conclusion: Cholinergic and EGF receptors may affect the MAPK pathway in K562 cells.
Conclusion: Cholinergic and EGF receptors may affect the MAPK pathway in K562 cells.
References
- Tansey EM. Henry Dale and the discovery of acetylcholine.
C R Biologie 2006; 329:419-25. doi: 10.1016/j.crvi.2006.03.012
- Fujii T, Mashimo M, Moriwaki Y, et al. Expression and
function of the cholinergic system in immune cells. Front
Immunol 2017;8: 1085. doi: 10.3389/fimmu.2017.01085ç.
- Van Koppen CJ, Kaiser B. Regulation of muscarinic
acetylcholine receptor signaling. Pharmacol Ther 2003;
98:197-220. doi: 10.1016/s0163-7258(03)00032-9.
- Caulfield MP, Birdsall NJ. International Union of Pharmacology.
XVII. Classification of muscarinic acetylcholine receptors.
Pharmacol Rev 1998; 50:279-90.
- Felder CC. Muscarinic acetylcholine receptors: Signal
transduction through multiple effectors. FASEB J 1995 ;9; 619-
25.
- Shah N, Khurana S, Cheng K, Raufman JP. Muscarinic
receptors and ligands in cancer. Am J Physiol Cell Physiol
2009; 296: C221-C232. doi: 10.1152/ajpcell.005 14. 2008.
- Nathanson MN. A multiplicity of muscarinic mechanisms:
Enough signalling pathways to take your breath away. Proc
Natl Acad Sci 2000 ;97, 6245-7. doi: 10.1073/pnas.97.12.6245
- Eglen RM, Hedge SS, Watson N. Muscarinic receptor subtypes
and smooth muscle function. Pharmacol Rev 1996; 48: 531-
65. PMID: 8981565.
- Gutkind JS. Regulation of mitogen-activated protein kinase
signaling networks by G protein-coupled receptors. Sci STKE.
2000 ;40:re1. doi: 10.1126/stke.2000.40.re1.
- Park YS, Cho NJ. EGFR and PKC are involved in the activation
of ERK1/2 and p90 RSK and the subsequent proliferation of
SNU-407 colon cancer cells by muscarinic acetylcholine
receptors. Mol Cell Biochem 2012 ;370:191-8. doi: 10.1007/
s11010.012.1410-z.
- Ukegawa JI, Takeuchi Y, Kusayanagi S, Mitamura K. Growthpromoting
effect of muscarinic acetylcholine receptors in
colon cancer cells. J Cancer Res Clin Oncol 2003 ;129:272-8.
doi: 10.1007/s00432.003.0433-y.
- Kolch W. Meaningful relationships: The regulation of the Ras/
Raf/MEK/ERK pathway by protein interactions. Biochem J
2000; 351:289-305.
- Rosenblum K, Futter M, Jones M, Hulme EC, Bliss TV.
ERKI/II regulation by the muscarinic acetylcholine receptors
in neurons. J Neurosci 2000; 20:977-85. doi: 10.1523/
JNEUROSCI.20-03-00977.2000
- Cabadak H, Kucukibrahimoglu E, Aydin B, Kan B, Zafer Goren
M. Muscarinic receptor-mediated nitric oxide release in a
K562 erythroleukaemia cell line. Auton Autacoid Pharmacol.
2009; 29:109-15. doi: 10.1111/j.1474-8673.2009.00431.x
- Cabadak H, Aydin B, Kan B. Regulation of M2, M3, and M4
muscarinic receptor expression in K562 chronic myelogenous
leukemia cells by carbachol. J Recept Signal Transd Res
2011;31: 26-32. doi: 10.3109/10799.893.2010.506484.
- Onder N, G, Aydin B, Cabadak, H. Studies on the role of alpha
7 nicotinic acetylcholine receptors in K562 cell proliferation
and signaling. Mol Biol Rep 2021; 48: 5045-55. doi: 10.1007/
s11033.021.06498-4.
- Liebmann C, Bohmer FD. Signal transduction pathways of G
protein-coupled receptors and their cross-talk with receptor
tyrosine kinases: Lessons from bradykinin signaling. Curr
Med Chem 2000 ; 7: 911-43. doi: 10.2174/092.986.7003374589
- Pearson G, Robinson F, Beers Gibson T, et al. Mitogenactivated
protein (MAP) kinase pathways: Regulation
and physiological functions. Endocr Rev 2001;22: 153-83.
doi:10.1210/edrv.22.2.0428
- Daub H, Wallasch C, Lankenau A, Herrlich A, Ullrich A. Signal
characteristics of G protein-transactivated EGF receptor.
EMBO J 1997 ;16: 7032-44. doi:10.1093/emboj/16.23.7032
- Cheng K. Zimniak P. Raufman JP. Transactivation of the
epidermal growth factor receptor mediates cholinergic
agonist-induced proliferation of h508 human colon cancer
cells. Cancer Res 2003 ;63: 6744-50.
- Nicke B, Detjen K, Logsdon C. Muscarinic cholinergic
receptors activate both inhibitory and stimulatory growth
mechanisms in NIH3T3 cells. J Biol Chem 1999; 274: 21701-6.
doi: 10.1074/jbc.274.31.21701
- Kuol N, Davidson M. Karakkat J, et al. Blocking muscarinic
receptor 3 attenuates tumor growth and decreases
immunosuppressive and cholinergic markers in an orthotopic
mouse model of colorectal cancer. Int J Mol Sci 2023; 24: 596.
doi: 10.3390 /ijms24010596
- Lanzafame A, Christopoulos A, Mitchelson F. Cellular
signaling mechanisms for muscarinic acetylcholine receptors.
Receptors Channels 2003; 9: 241-60.
- Metzger M, Just L, Boss A, Drews U. Identification and
functional characterization of the muscarinic receptor M3 in
the human keratinocyte cell line haCat. Cells Tissues Organs
2005;180: 96-105. doi: 10.1159/000086750.
- Prenzel N, Zwick E, Daub H, et al. EGF receptor transactivation
by G-protein-coupled receptors requires metalloproteinase
cleavage of proHB-EGF. Nature 1999; 402: 884-8. doi:
10.1038/47260
- Yu H, Xia H, Tang Q, et al., Acetylcholine acts through M3
muscarinic receptor to activate the EGFR signaling and
promotes gastric cancer cell proliferation. Sci Rep 2017; 7:
40802. doi: 10.1038/srep40802.
- Yang T, He W, Cui F, et al. MACC1 mediates acetylcholineinduced
invasion and migration by human gastric cancer
cells. Oncotarget 2016; 7: 18085-94. doi: 10.18632/
oncotarget.7634.
- Lan L, Wang H, Yang R, et al. R2-8018 reduces the proliferation
and migration of non-small cell lung cancer cells by disturbing
transactivation between M3R and EGFR. Life Sci 2019 ; 234:
116742. doi: 10.1016/j.lfs.2019.116742.
- Calaf GM, Crispin LA, Muñoz JP, Aguayo F, Bleak TC. Muscarinic
receptors associated with cancer. Cancers 2022;14:2322.
doi:10.3390/cancers14092322
- Kanlı Z, Cabadak H, Aydın B. Potential antiproliferative and
apoptotic effects of pilocarpine combined with TNF alpha
in chronic myeloid leukemia cells. Naunyn Schmiedebergs
Arch Pharmacol 2023; 396: 1513-24 doi.org/10.1007/
s00210.023.02418-4 .
- Kanlı Z, Aydın B, Cabadak H. Effects of several compounds
in human erythroleukemia K562 cell proliferation and
apoptosis. Marmara Med J 2019; 32:20-26. doi.org/10.5472/
marumj.518797
- Aydin B, Tulunay A, Ekşioğlu-Demiralp E, Kan B, Cabadak
H. Effects of carbachol on apoptosis in human chronic
myelogenous leukemic K562 cell line. Marmara Med J 2019;
32: 38-43. doi.org 10.5472/marumj.518983.
Year 2024,
, 86 - 91, 28.01.2024
Selda Güler Atmaca
,
Banu Aydın
,
Hulya Cabadak
References
- Tansey EM. Henry Dale and the discovery of acetylcholine.
C R Biologie 2006; 329:419-25. doi: 10.1016/j.crvi.2006.03.012
- Fujii T, Mashimo M, Moriwaki Y, et al. Expression and
function of the cholinergic system in immune cells. Front
Immunol 2017;8: 1085. doi: 10.3389/fimmu.2017.01085ç.
- Van Koppen CJ, Kaiser B. Regulation of muscarinic
acetylcholine receptor signaling. Pharmacol Ther 2003;
98:197-220. doi: 10.1016/s0163-7258(03)00032-9.
- Caulfield MP, Birdsall NJ. International Union of Pharmacology.
XVII. Classification of muscarinic acetylcholine receptors.
Pharmacol Rev 1998; 50:279-90.
- Felder CC. Muscarinic acetylcholine receptors: Signal
transduction through multiple effectors. FASEB J 1995 ;9; 619-
25.
- Shah N, Khurana S, Cheng K, Raufman JP. Muscarinic
receptors and ligands in cancer. Am J Physiol Cell Physiol
2009; 296: C221-C232. doi: 10.1152/ajpcell.005 14. 2008.
- Nathanson MN. A multiplicity of muscarinic mechanisms:
Enough signalling pathways to take your breath away. Proc
Natl Acad Sci 2000 ;97, 6245-7. doi: 10.1073/pnas.97.12.6245
- Eglen RM, Hedge SS, Watson N. Muscarinic receptor subtypes
and smooth muscle function. Pharmacol Rev 1996; 48: 531-
65. PMID: 8981565.
- Gutkind JS. Regulation of mitogen-activated protein kinase
signaling networks by G protein-coupled receptors. Sci STKE.
2000 ;40:re1. doi: 10.1126/stke.2000.40.re1.
- Park YS, Cho NJ. EGFR and PKC are involved in the activation
of ERK1/2 and p90 RSK and the subsequent proliferation of
SNU-407 colon cancer cells by muscarinic acetylcholine
receptors. Mol Cell Biochem 2012 ;370:191-8. doi: 10.1007/
s11010.012.1410-z.
- Ukegawa JI, Takeuchi Y, Kusayanagi S, Mitamura K. Growthpromoting
effect of muscarinic acetylcholine receptors in
colon cancer cells. J Cancer Res Clin Oncol 2003 ;129:272-8.
doi: 10.1007/s00432.003.0433-y.
- Kolch W. Meaningful relationships: The regulation of the Ras/
Raf/MEK/ERK pathway by protein interactions. Biochem J
2000; 351:289-305.
- Rosenblum K, Futter M, Jones M, Hulme EC, Bliss TV.
ERKI/II regulation by the muscarinic acetylcholine receptors
in neurons. J Neurosci 2000; 20:977-85. doi: 10.1523/
JNEUROSCI.20-03-00977.2000
- Cabadak H, Kucukibrahimoglu E, Aydin B, Kan B, Zafer Goren
M. Muscarinic receptor-mediated nitric oxide release in a
K562 erythroleukaemia cell line. Auton Autacoid Pharmacol.
2009; 29:109-15. doi: 10.1111/j.1474-8673.2009.00431.x
- Cabadak H, Aydin B, Kan B. Regulation of M2, M3, and M4
muscarinic receptor expression in K562 chronic myelogenous
leukemia cells by carbachol. J Recept Signal Transd Res
2011;31: 26-32. doi: 10.3109/10799.893.2010.506484.
- Onder N, G, Aydin B, Cabadak, H. Studies on the role of alpha
7 nicotinic acetylcholine receptors in K562 cell proliferation
and signaling. Mol Biol Rep 2021; 48: 5045-55. doi: 10.1007/
s11033.021.06498-4.
- Liebmann C, Bohmer FD. Signal transduction pathways of G
protein-coupled receptors and their cross-talk with receptor
tyrosine kinases: Lessons from bradykinin signaling. Curr
Med Chem 2000 ; 7: 911-43. doi: 10.2174/092.986.7003374589
- Pearson G, Robinson F, Beers Gibson T, et al. Mitogenactivated
protein (MAP) kinase pathways: Regulation
and physiological functions. Endocr Rev 2001;22: 153-83.
doi:10.1210/edrv.22.2.0428
- Daub H, Wallasch C, Lankenau A, Herrlich A, Ullrich A. Signal
characteristics of G protein-transactivated EGF receptor.
EMBO J 1997 ;16: 7032-44. doi:10.1093/emboj/16.23.7032
- Cheng K. Zimniak P. Raufman JP. Transactivation of the
epidermal growth factor receptor mediates cholinergic
agonist-induced proliferation of h508 human colon cancer
cells. Cancer Res 2003 ;63: 6744-50.
- Nicke B, Detjen K, Logsdon C. Muscarinic cholinergic
receptors activate both inhibitory and stimulatory growth
mechanisms in NIH3T3 cells. J Biol Chem 1999; 274: 21701-6.
doi: 10.1074/jbc.274.31.21701
- Kuol N, Davidson M. Karakkat J, et al. Blocking muscarinic
receptor 3 attenuates tumor growth and decreases
immunosuppressive and cholinergic markers in an orthotopic
mouse model of colorectal cancer. Int J Mol Sci 2023; 24: 596.
doi: 10.3390 /ijms24010596
- Lanzafame A, Christopoulos A, Mitchelson F. Cellular
signaling mechanisms for muscarinic acetylcholine receptors.
Receptors Channels 2003; 9: 241-60.
- Metzger M, Just L, Boss A, Drews U. Identification and
functional characterization of the muscarinic receptor M3 in
the human keratinocyte cell line haCat. Cells Tissues Organs
2005;180: 96-105. doi: 10.1159/000086750.
- Prenzel N, Zwick E, Daub H, et al. EGF receptor transactivation
by G-protein-coupled receptors requires metalloproteinase
cleavage of proHB-EGF. Nature 1999; 402: 884-8. doi:
10.1038/47260
- Yu H, Xia H, Tang Q, et al., Acetylcholine acts through M3
muscarinic receptor to activate the EGFR signaling and
promotes gastric cancer cell proliferation. Sci Rep 2017; 7:
40802. doi: 10.1038/srep40802.
- Yang T, He W, Cui F, et al. MACC1 mediates acetylcholineinduced
invasion and migration by human gastric cancer
cells. Oncotarget 2016; 7: 18085-94. doi: 10.18632/
oncotarget.7634.
- Lan L, Wang H, Yang R, et al. R2-8018 reduces the proliferation
and migration of non-small cell lung cancer cells by disturbing
transactivation between M3R and EGFR. Life Sci 2019 ; 234:
116742. doi: 10.1016/j.lfs.2019.116742.
- Calaf GM, Crispin LA, Muñoz JP, Aguayo F, Bleak TC. Muscarinic
receptors associated with cancer. Cancers 2022;14:2322.
doi:10.3390/cancers14092322
- Kanlı Z, Cabadak H, Aydın B. Potential antiproliferative and
apoptotic effects of pilocarpine combined with TNF alpha
in chronic myeloid leukemia cells. Naunyn Schmiedebergs
Arch Pharmacol 2023; 396: 1513-24 doi.org/10.1007/
s00210.023.02418-4 .
- Kanlı Z, Aydın B, Cabadak H. Effects of several compounds
in human erythroleukemia K562 cell proliferation and
apoptosis. Marmara Med J 2019; 32:20-26. doi.org/10.5472/
marumj.518797
- Aydin B, Tulunay A, Ekşioğlu-Demiralp E, Kan B, Cabadak
H. Effects of carbachol on apoptosis in human chronic
myelogenous leukemic K562 cell line. Marmara Med J 2019;
32: 38-43. doi.org 10.5472/marumj.518983.