Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin. / Li, Hongbing; Panina, Svetlana; Kaur, Amandeep; Ruano, María J.; Sánchez-González, Pablo; la Cour, Peter Jonas Marstrand; Stephan, Alexander; Olesen, Uffe Høgh; Berchtold, Martin Werner; Villalobo, Antonio.

In: Journal of Biological Chemistry, Vol. 287, No. 5, 2012, p. 3273-3281.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Li, H, Panina, S, Kaur, A, Ruano, MJ, Sánchez-González, P, la Cour, PJM, Stephan, A, Olesen, UH, Berchtold, MW & Villalobo, A 2012, 'Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin', Journal of Biological Chemistry, vol. 287, no. 5, pp. 3273-3281. https://doi.org/10.1074/jbc.M111.317529

APA

Li, H., Panina, S., Kaur, A., Ruano, M. J., Sánchez-González, P., la Cour, P. J. M., Stephan, A., Olesen, U. H., Berchtold, M. W., & Villalobo, A. (2012). Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin. Journal of Biological Chemistry, 287(5), 3273-3281. https://doi.org/10.1074/jbc.M111.317529

Vancouver

Li H, Panina S, Kaur A, Ruano MJ, Sánchez-González P, la Cour PJM et al. Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin. Journal of Biological Chemistry. 2012;287(5):3273-3281. https://doi.org/10.1074/jbc.M111.317529

Author

Li, Hongbing ; Panina, Svetlana ; Kaur, Amandeep ; Ruano, María J. ; Sánchez-González, Pablo ; la Cour, Peter Jonas Marstrand ; Stephan, Alexander ; Olesen, Uffe Høgh ; Berchtold, Martin Werner ; Villalobo, Antonio. / Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 5. pp. 3273-3281.

Bibtex

@article{a47c33bb73bf4bb98eeb2c9b4227958a,
title = "Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin",
abstract = "Calmodulin (CaM) is the major component ofcalcium signaling pathways mediating theaction of various effectors. Transient increasesin the intracellular calcium level triggered by avariety of stimuli lead to the formation ofCa2+/CaM complexes, which interact with andactivate target proteins. In the present studythe role of Ca2+/CaM in the regulation of theligand-dependent activation of the epidermalgrowth factor receptor (EGFR) has beenexamined in living cells. We show that additionof different cell permeable CaM antagonists tocultured cells or loading cells with a Ca2+chelator inhibited ligand-dependent EGFRauto(trans)phosphorylation. This occurred alsoin the presence of inhibitors of protein kinaseC, CaM-dependent protein kinase II andcalcineurin, which are known Ca2+- and/orCa2+/CaM-dependent EGFR regulators,pointing to a direct effect of Ca2+/CaM on thereceptor. Furthermore, we demonstrate thatdown-regulation of CaM in conditional CaMknock out cells stably transfected with thehuman EGFR decreased its ligand-dependentphosphorylation. Substitution of six basicamino acid residues within the CaM-bindingdomain (CaM-BD) of the EGFR by alanineresulted in a decreased phosphorylation of thereceptor and of its downstream substratephospholipase C¿1. These results support thehypothesis that Ca2+/CaM regulates the EGFRactivity by directly interacting with the CaMBDof the receptor located at its cytosolicjuxtamembrane region.",
author = "Hongbing Li and Svetlana Panina and Amandeep Kaur and Ruano, {Mar{\'i}a J.} and Pablo S{\'a}nchez-Gonz{\'a}lez and {la Cour}, {Peter Jonas Marstrand} and Alexander Stephan and Olesen, {Uffe H{\o}gh} and Berchtold, {Martin Werner} and Antonio Villalobo",
year = "2012",
doi = "10.1074/jbc.M111.317529",
language = "English",
volume = "287",
pages = "3273--3281",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin

AU - Li, Hongbing

AU - Panina, Svetlana

AU - Kaur, Amandeep

AU - Ruano, María J.

AU - Sánchez-González, Pablo

AU - la Cour, Peter Jonas Marstrand

AU - Stephan, Alexander

AU - Olesen, Uffe Høgh

AU - Berchtold, Martin Werner

AU - Villalobo, Antonio

PY - 2012

Y1 - 2012

N2 - Calmodulin (CaM) is the major component ofcalcium signaling pathways mediating theaction of various effectors. Transient increasesin the intracellular calcium level triggered by avariety of stimuli lead to the formation ofCa2+/CaM complexes, which interact with andactivate target proteins. In the present studythe role of Ca2+/CaM in the regulation of theligand-dependent activation of the epidermalgrowth factor receptor (EGFR) has beenexamined in living cells. We show that additionof different cell permeable CaM antagonists tocultured cells or loading cells with a Ca2+chelator inhibited ligand-dependent EGFRauto(trans)phosphorylation. This occurred alsoin the presence of inhibitors of protein kinaseC, CaM-dependent protein kinase II andcalcineurin, which are known Ca2+- and/orCa2+/CaM-dependent EGFR regulators,pointing to a direct effect of Ca2+/CaM on thereceptor. Furthermore, we demonstrate thatdown-regulation of CaM in conditional CaMknock out cells stably transfected with thehuman EGFR decreased its ligand-dependentphosphorylation. Substitution of six basicamino acid residues within the CaM-bindingdomain (CaM-BD) of the EGFR by alanineresulted in a decreased phosphorylation of thereceptor and of its downstream substratephospholipase C¿1. These results support thehypothesis that Ca2+/CaM regulates the EGFRactivity by directly interacting with the CaMBDof the receptor located at its cytosolicjuxtamembrane region.

AB - Calmodulin (CaM) is the major component ofcalcium signaling pathways mediating theaction of various effectors. Transient increasesin the intracellular calcium level triggered by avariety of stimuli lead to the formation ofCa2+/CaM complexes, which interact with andactivate target proteins. In the present studythe role of Ca2+/CaM in the regulation of theligand-dependent activation of the epidermalgrowth factor receptor (EGFR) has beenexamined in living cells. We show that additionof different cell permeable CaM antagonists tocultured cells or loading cells with a Ca2+chelator inhibited ligand-dependent EGFRauto(trans)phosphorylation. This occurred alsoin the presence of inhibitors of protein kinaseC, CaM-dependent protein kinase II andcalcineurin, which are known Ca2+- and/orCa2+/CaM-dependent EGFR regulators,pointing to a direct effect of Ca2+/CaM on thereceptor. Furthermore, we demonstrate thatdown-regulation of CaM in conditional CaMknock out cells stably transfected with thehuman EGFR decreased its ligand-dependentphosphorylation. Substitution of six basicamino acid residues within the CaM-bindingdomain (CaM-BD) of the EGFR by alanineresulted in a decreased phosphorylation of thereceptor and of its downstream substratephospholipase C¿1. These results support thehypothesis that Ca2+/CaM regulates the EGFRactivity by directly interacting with the CaMBDof the receptor located at its cytosolicjuxtamembrane region.

U2 - 10.1074/jbc.M111.317529

DO - 10.1074/jbc.M111.317529

M3 - Journal article

C2 - 22157759

VL - 287

SP - 3273

EP - 3281

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -

ID: 38118524