The role of the calmodulin-binding and calmodulin-like domains of the epidermal growth factor receptor in tyrosine kinase activation.
Animals
CHO Cells
Calcium Signaling
/ physiology
Calmodulin
/ metabolism
Cell Line
Cell Membrane
/ metabolism
Cricetulus
Enzyme Activation
/ physiology
Epidermal Growth Factor
/ metabolism
ErbB Receptors
/ genetics
Humans
Protein Binding
/ physiology
Protein Domains
/ physiology
Protein-Tyrosine Kinases
/ metabolism
calmodulin
calmodulin-binding domain
calmodulin-like domain
epidermal growth factor receptor
receptor internalization
tyrosine kinase activity
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
20
11
2020
received:
05
08
2020
accepted:
26
11
2020
pubmed:
12
12
2020
medline:
15
10
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
The epidermal growth factor receptor (EGFR) harbors a calmodulin (CaM)-binding domain (CaM-BD) and a CaM-like domain (CaM-LD) upstream and downstream, respectively, of the tyrosine kinase (TK) domain. We demonstrate in this paper that deletion of the positively charged CaM-BD (EGFR/CaM-BD∆) inactivated the TK activity of the receptor. Moreover, deletion of the negatively charged CaM-LD (EGFR/CaM-LD∆), leaving a single negative residue (glutamate), reduced the activity of the receptor. In contrast, substituting the CaM-LD with a histidine/valine-rich peptide (EGFR/InvCaM-LD) caused full inactivation. We also demonstrated using confocal microscopy and flow cytometry that the chimera EGFR-green fluorescent protein (GFP)/CaM-BD∆, the EGFR/CaM-LD∆, and EGFR/InvCaM-LD mutants all bind tetramethylrhodamine-labelled EGF. These EGFR mutants were localized at the plasma membrane as the wild-type receptor does. However, only the EGFR/CaM-LD∆ and EGFR/InvCaM-LD mutants appear to undergo ligand-dependent internalization, while the EGFR-GFP/CaM-BD∆ mutant seems to be deficient in this regard. The obtained results and in silico modelling studies of the asymmetric structure of the EGFR kinase dimer support a role of a CaM-BD/CaM-LD electrostatic interaction in the allosteric activation of the EGFR TK.
Substances chimiques
Calmodulin
0
Epidermal Growth Factor
62229-50-9
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4997-5011Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Aifa, S., Aydin, J., Nordvall, G., Lundström, I., Svensson, S. P. S., & Hermanson, O. (2005). A basic peptide within the juxtamembrane region is required for EGF receptor dimerization. Experimental Cell Research, 302, 108-114. https://doi.org/10.1016/j.yexcr.2004.08.032
Aifa, S., Frikha, F., Miled, N., Johansen, K., Lundström, I., & Svensson, S. P. S. (2006). Phosphorylation of Thr654 but not Thr669 within the juxtamembrane domain of the EGF receptor inhibits calmodulin binding. Biochemical and Biophysical Research Communications, 347(2), 381-387. https://doi.org/10.1016/j.bbrc.2006.05.200
Aifa, S., Johansen, K., Nilsson, U. K., Liedberg, B., Lundström, I., & Svensson, S. P. S. (2002). Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance. Cellular Signalling, 14(12), 1005-1013. https://doi.org/10.1016/S0898-6568(02)00034-7
Alcalde, J., González-Muñoz, M., & Villalobo, A. (2020). Grb7-derived calmodulin-binding peptides inhibit proliferation, migration and invasiveness of tumor cells while they enhance attachment to the substrate. Heliyon, 6(5):e03922. https://doi.org/10.1016/j.heliyon.2020.e03922
Alroy, I., & Yarden, Y. (1997). The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Letters, 410(1), 83-86. https://doi.org/10.1016/S0014-5793(97)00412-2
Boran, A. D. W., Seco, J., Jayaraman, V., Jayaraman, G., Zhao, S., Reddy, S., Chen, Y., & Iyengar, R. (2012). A potential peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor. PLoS One, 7, e49702. https://doi.org/10.1371/journal.pone.0049702
Carpenter, G. (1987). Receptors for epidermal growth factor and other polypeptide mitogens. Annual Review of Biochemistry, 56(1), 881-914. https://doi.org/10.1146/annurev.bi.56.070187.004313
Citri, A., & Yarden, Y. (2006). EGF-ERBB signalling: Towards the systems level. Nature Reviews Molecular Cell Biology, 7(7), 505-516. https://doi.org/10.1038/nrm1962
Forbes, K., Skinner, L., Aplin, J. D., & Westwood, M. (2012). The tyrosine phosphatase SHP-1 negatively regulates cytotrophoblast proliferation in first-trimester human placenta by modulating EGFR activation. Cellular and Molecular Life Sciences, 69(23), 4029-4040. https://doi.org/10.1007/s00018-012-1067-5
Garrett, T. P. J., McKern, N. M., Lou, M., Elleman, T. C., Adams, T. E., Lovrecz, G. O., Zhu, H. J., Walker, F., Frenkel, M. J., Hoyne, P. A., Jorissen, R. N., Nice, E. C., Burgess, A. W., & Ward, C. W. (2002). Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor α. Cell, 110, 763-773. https://doi.org/10.1016/S0092-8674(02)00940-6
Hack, N., Margolis, B., Schlessinger, J., & Skorecki, K. (1991). Interaction of epidermal growth factor with vasoac11ve hormones in the regulation of phospholipase a2. Journal of Basic and Clinical Physiology and Pharmacology, 2(3), 161-182. https://doi.org/10.1515/JBCPP.1991.2.3.161.
Hackel, P. O., Gishizky, M., & Ullrich, A. (2001). Mig-6 is a negative regulator of the epidermal growth factor receptor signal. Biological Chemistry, 382(12), 1649-1662. https://doi.org/10.1515/BC.2001.200
Han, J. M., Kim, Y., Lee, J. S., Lee, C. S., Lee, B. D., Ohba, M., Kuroki, T., Suh, P.-G., & Ryu, S. H. (2002). Localization of phospholipase D1 to caveolin-enriched membrane via palmitoylation: Implications for epidermal growth factor signaling. Molecular Biology of the Cell, 13(11), 3976-3988. https://doi.org/10.1091/mbc.e02-02-0100
Harmon, A. C., Yoo, B. C., & McCaffery, C. (1994). Pseudosubstrate inhibition of CDPK, a protein kinase with a calmodulin-like domain. Biochemistry, 33, 7278-7287. https://doi.org/10.1021/bi00189a032
Harper, J. F., Huang, J.-F., & Lloyd, S. J. (1994). Genetic identification of an autoinhibitor in CDPK, a protein kinase with a calmodulin-like domain. Biochemistry, 33(23), 7267-7277. https://doi.org/10.1021/bi00189a031
Harris, R. (2003). EGF receptor ligands. Experimental Cell Research, 284(1), 2-13. https://doi.org/10.1016/S0014-4827(02)00105-2
Hart, M. R., Su, H.-Y., Broka, D., Goverdhan, A., & Schroeder, J. A. (2013). Inactive ERBB receptors cooperate with reactive oxygen species to suppress cancer progression. Molecular Therapy, 21(11), 1996-2007. https://doi.org/10.1038/mt.2013.196
Haugh, J. M., Schooler, K., Wells, A., Wiley, H. S., & Lauffenburger, D. A. (1999). Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-γ1 signaling pathway. Journal of Biological Chemistry, 274(13), 8958-8965. https://doi.org/10.1074/jbc.274.13.8958
Hrabak, E. M., Dickmann, L. J., Satterlee, J. S., & Sussman, M. R. (1996). Characterization of eight new members of the calmodulin-like domain protein kinase gene family from Arabidopsis thaliana. Plant Molecular Biology, 31(2), 405-412. https://doi.org/10.1007/BF00021802
Hsu, S.-C., & Hung, M.-C. (2007). Characterization of a novel tripartite nuclear localization sequence in the EGFR Family. Journal of Biological Chemistry, 282(14), 10432-10440. https://doi.org/10.1074/jbc.M610014200
Hubbard, S. R. (2004). Juxtamembrane autoinhibition in receptor tyrosine kinases. Nature Reviews Molecular Cell Biology, 5(6), 464-471. https://doi.org/10.1038/nrm1399
Jorissen, R. N., Walker, F., Pouliot, N., Garrett, T. P. J., Ward, C. W., & Burgess, A. W. (2003). Epidermal growth factor receptor: Mechanisms of activation and signalling. In. Experimental Cell Research, 284, 31-53. https://doi.org/10.1016/S0014-4827(02)00098-8
Jura, N., Endres, N. F., Engel, K., Deindl, S., Das, R., Lamers, M. H., Wemmer, D. E., Zhang, X., & Kuriyan, J. (2009). Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell, 137(7), 1293-1307. https://doi.org/10.1016/j.cell.2009.04.025
Landau, M., Fleishman, S. J., & Ben-Tal, N. (2004). A putative mechanism for downregulation of the catalytic activity of the EGF receptor via direct contact between its kinase and C-terminal domains. Structure, 12, 2265-2275. https://doi.org/10.1016/j.str.2004.10.006
Lemmon, M. A., & Schlessinger, J. (2010). Cell signaling by receptor tyrosine kinases. In Cell, 141, 1117-1134. https://doi.org/10.1016/j.cell.2010.06.011
Li, H., Panina, S., Kaur, A., Ruano, M. J., Sánchez-González, P., la Cour, 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
Li, H., Ruano, M. J., & Villalobo, A. (2004). Endogenous calmodulin interacts with the epidermal growth factor receptor in living cells. FEBS Letters, 559(1-3), 175-180. https://doi.org/10.1016/S0014-5793(04)00067-5
Li, N., Schlessinger, J., & Margolis, B. (1994). Autophosphorylation mutants of the EGF-receptor signal through auxiliary mechanisms involving SH2 domain proteins. Oncogene, 9, 3457-3465.
Lin, S. Y., Makino, K., Xia, W., Matin, A., Wen, Y., Kwong, K. Y., Bourguignon, L., & Hung, M. C. (2001). Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nature Cell Biology, 3, 802-808https://doi.org/10.1038/ncb0901-802
Martín-Nieto, J., Cusidó-Hita, D. M., Li, H., Benguría, A., & Villalobo, A. (2002). Regulation of ErbB receptors by calmodulin. Recent Res. Recent Research Developments in Biochemistry, 3, 41-58.
Martín-Nieto, J., & Villalobo, A. (1998). The human epidermal growth factor receptor contains a juxtamembrane calmodulin-binding site†. Biochemistry, 37(1), 227-236. https://doi.org/10.1021/bi971765v
Mattila, E., Pellinen, T., Nevo, J., Vuoriluoto, K., Arjonen, A., & Ivaska, J. (2005). Negative regulation of EGFR signalling through integrin-α1β1-mediated activation of protein tyrosine phosphatase TCPTP. Nature Cell Biology, 7(1), 78-85. https://doi.org/10.1038/ncb1209
McLaughlin, S., Smith, S. O., Hayman, M. J., & Murray, D. (2005). An electrostatic engine model for autoinhibition and activation of the epidermal growth factor receptor (EGFR/ErbB) family. Journal of General Physiology, 126, 41-53. https://doi.org/10.1085/jgp.200509274
Ogiso, H., Ishitani, R., Nureki, O., Fukai, S., Yamanaka, M., Kim, J. H., Saito, K., Sakamoto, A., Inoue, M., Shirouzu, M., & Yokoyama, S. (2002). Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell, 110, 775-787. https://doi.org/10.1016/S0092-8674(02)00963-7
Poppleton, H. M., Sun, H., Mullenix, J. B., Wiepz, G. J., Bertics, P. J., & Patel, T. B. (2000). The juxtamembrane region of the epidermal growth factor receptor is required for phosphorylation of Gα(s). Archives of Biochemistry and Biophysics, 383, 309-317. https://doi.org/10.1006/abbi.2000.2095
Red Brewer, M., Choi, S. H., Alvarado, D., Moravcevic, K., Pozzi, A., Lemmon, M. A., & Carpenter, G. (2009). The juxtamembrane region of the EGF receptor functions as an activation domain. Molecular Cell, 34(6), 641-651. https://doi.org/10.1016/j.molcel.2009.04.034
Reschke, M., Ferby, I., Stepniak, E., Seitzer, N., Horst, D., Wagner, E. F., & Ullrichi, A. (2010). Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor receptor signaling in hepatocytes and human hepatocellular carcinoma. Hepatology, 51, 1383-1390. https://doi.org/10.1002/hep.23428
Ruff-Jamison, S., Chen, K., & Cohen, S. (1995). Epidermal growth factor induces the tyrosine phosphorylation and nuclear translocation of Stat 5 in mouse liver Proceedings of the National Academy of Sciences. 92(10), 4215-4218. https://doi.org/10.1073/pnas.92.10.4215
Salcini, A. E., Chen, H., Iannolo, G., De Camilli, P., & Di Fiore, P. P. (1999). Epidermal growth factor pathway substrate 15, Eps15. The International Journal of Biochemistry & Cell Biology, 31(8), 805-809. https://doi.org/10.1016/S1357-2725(99)00042-4
Sánchez-González, P., Jellali, K., & Villalobo, A. (2010). Calmodulin-mediated regulation of the epidermal growth factor receptor. FEBS Journal, 277(2), 327-342. https://doi.org/10.1111/j.1742-4658.2009.07469.x
Sato, T., Pallavi, P., Golebiewska, U., McLaughlin, S., & Smith, S. O. (2006). Structure of the membrane reconstituted transmembrane-juxtamembrane peptide EGFR(622-660) and its interaction with Ca2+/Calmodulin. Biochemistry, 45, 12704-12714. https://doi.org/10.1021/bi061264m
Schäfer, B., Gschwind, A., & Ullrich, A. (2004). Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene, 23(4), 991-999. https://doi.org/10.1038/sj.onc.1207278
Sengupta, P., Ruano, M. J., Tebar, F., Golebiewska, U., Zaitseva, I., Enrich, C., McLaughlin, S., & Villalobo, A. (2007). Membrane-permeable calmodulin inhibitors (e.g. W-7/W-13) Bind to membranes, changing the electrostatic surface potential. Journal of Biological Chemistry, 282(11), 8474-8486. https://doi.org/10.1074/jbc.M607211200
Stamos, J., Sliwkowski, M. X., & Eigenbrot, C. (2002). Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. Journal of Biological Chemistry, 277, 46265-46272. https://doi.org/10.1074/jbc.M207135200
Stateva, S. R., Salas, V., Benguría, A., Cossío, I., Anguita, E., Martín-Nieto, J., Benaim, G., & Villalobo, A. (2015). The activating role of phospho-(Tyr)-calmodulin on the epidermal growth factor receptor. Biochemical Journal, 472(2), 195-204. https://doi.org/10.1042/BJ20150851
Thiel, K. W., & Carpenter, G. (2007). Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation. Proceedings of the National Academy of Sciences, 104(49), 19238-19243. https://doi.org/10.1073/pnas.0703854104
Thien, C. B. F., & Langdon, W. Y. (2005). c-Cbl and Cbl-b ubiquitin ligases: Substrate diversity and the negative regulation of signalling responses. In Biochemical Journal. 391, 153-166. https://doi.org/10.1042/BJ20050892
Villalobo, A. (2018). The multifunctional role of phospho-calmodulin in pathophysiological processes. Biochemical Journal, 475(24), 4011-4023. https://doi.org/10.1042/BCJ20180755
Villalobo, A., García-Palmero, I., Stateva, S. R., & Jellali, K. (2013). Targeting the calmodulin-regulated ErbB/Grb7 signaling axis in cancer therapy. Journal of Pharmacy & Pharmaceutical Sciences, 16(2), 177. https://doi.org/10.18433/J3V59V
Villalobo, A., González-Muñoz, M., & Berchtold, M. W. (2019). Proteins with calmodulin-like domains: Structures and functional roles. Cellular and Molecular Life Sciences: CMLS, 76(12), 2299-2328. https://doi.org/10.1007/s00018-019-03062-z
Villalobo, A., Ruano, M. J., Palomo-Jiménez, P. I., Li, H., & Martín-Nieto, J. (2000). The epidermal growth factor receptor and the calcium signal. In Calcium: The molecular basis of calcium action in biology and medicine (pp. 287-303). Kluwer Academic Publishers.
Wahl, M. I., Nishibe, S., Suh, P. G., Rhee, S. G., & Carpenter, G. (1989). Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium. Proceedings of the National Academy of Sciences, 86(5), 1568-1572. https://doi.org/10.1073/pnas.86.5.1568
Watterson, D. M., Sharief, F., & Vanaman, T. C. (1980). The complete amino acid sequence of the Ca2+-dependent modulator protein (calmodulin) of bovine brain. Journal of Biological Chemistry, 255, 962-975.
Yamane, K., Toyoshima, C., & Nishimura, S. (1992). Ligand-induced functions of the epidermal growth factor receptor require the positively charged region asymmetrically distributed across plasma membrane. Biochemical and Biophysical Research Communications, 184(3), 1301-1310. https://doi.org/10.1016/S0006-291X(05)80024-5
Zhang, X., Gureasko, J., Shen, K., Cole, P. A., & Kuriyan, J. (2006). An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell, 125(6), 1137-1149. https://doi.org/10.1016/j.cell.2006.05.013
Zhang, X., Pickin, K. A., Bose, R., Jura, N., Cole, P. A., & Kuriyan, J. (2007). Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface. Nature, 450(7170), 741-744. https://doi.org/10.1038/nature05998
Zhong, Z., Wen, Z., & Darnell, J. E. (1994). Stat3: A STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science, 264, 95-98. https://doi.org/10.1126/science.8140422