![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 13, Issue 6, 2057-2068, June 2002
and
*Departament de Biologia Cel·lular, Facultat de Medicina,
Institut d'Investigacions August Pi i Sunyer (IDIBAPS), Universitat de
Barcelona, Barcelona, Spain 08036; and The epidermal growth factor receptor (EGFR) is a member of the
tyrosine kinase receptor family involved in signal transduction and the
regulation of cellular proliferation and differentiation. It is also a
calmodulin-binding protein. To examine the role of calmodulin in the
regulation of EGFR, the effect of calmodulin antagonist, W-13, on the
intracellular trafficking of EGFR and the MAPK signaling pathway was
analyzed. W-13 did not alter the internalization of EGFR but inhibited
its recycling and degradation, thus causing the accumulation of EGF and
EGFR in enlarged early endosomal structures. In addition, we
demonstrated that W-13 stimulated the tyrosine phosphorylation of EGFR
and consequent recruitment of Shc adaptor protein with EGFR, presumably
through inhibition of the calmodulin-dependent protein kinase II (CaM
kinase II). W-13-mediated EGFR phosphorylation was blocked by
metalloprotease inhibitor, BB94, indicating a possible involvement of
shedding in this process. However, MAPK activity was decreased by W-13; dissection of this signaling pathway showed that W-13 specifically interferes with Raf-1 activity. These data are consistent with the
regulation of EGFR by calmodulin at several steps of the receptor signaling and trafficking pathways.
Department of
Pharmacology, University of Colorado, Health Science Center, Denver,
Colorado 80262
Corresponding author. E-mail address:
enrich{at}medicina.ub.es.
This article has been cited by other articles:
|
|
 |
|
  L. Cubells, S. V. de Muga, F. Tebar, J. V. Bonventre, J. Balsinde, A. Pol, T. Grewal, and C. Enrich Annexin A6-induced Inhibition of Cytoplasmic Phospholipase A2 Is Linked to Caveolin-1 Export from the Golgi J. Biol. Chem., April 11, 2008; 283(15): 10174 - 10183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Llado, P. Timpson, S. Vila de Muga, J. Moreto, A. Pol, T. Grewal, R. J. Daly, C. Enrich, and F. Tebar Protein Kinase C{delta} and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin Mol. Biol. Cell, January 1, 2008; 19(1): 17 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Perry, H. Le, and I. I. Grichtchenko ANG II and calmodulin/CaMKII regulate surface expression and functional activity of NBCe1 via separate means Am J Physiol Renal Physiol, July 1, 2007; 293(1): F68 - F77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sengupta, M. J. Ruano, F. Tebar, U. Golebiewska, I. Zaitseva, C. Enrich, S. McLaughlin, and A. Villalobo Membrane-permeable Calmodulin Inhibitors (e.g. W-7/W-13) Bind to Membranes, Changing the Electrostatic Surface Potential: DUAL EFFECT OF W-13 ON EPIDERMAL GROWTH FACTOR RECEPTOR ACTIVATION J. Biol. Chem., March 16, 2007; 282(11): 8474 - 8486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Turner and J. R. Raymond Interaction of Calmodulin with the Serotonin 5-Hydroxytryptamine2A Receptor: A PUTATIVE REGULATOR OF G PROTEIN COUPLING AND RECEPTOR PHOSPHORYLATION BY PROTEIN KINASE C J. Biol. Chem., September 2, 2005; 280(35): 30741 - 30750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Choowongkomon, C. R. Carlin, and F. D. Sonnichsen A Structural Model for the Membrane-bound Form of the Juxtamembrane Domain of the Epidermal Growth Factor Receptor J. Biol. Chem., June 24, 2005; 280(25): 24043 - 24052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Gardiner, J. F. Arthur, M. L. Kahn, M. C. Berndt, and R. K. Andrews Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase Blood, December 1, 2004; 104(12): 3611 - 3617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Valiathan and M. D. Resh Expression of Human Immunodeficiency Virus Type 1 Gag Modulates Ligand-Induced Downregulation of EGF Receptor J. Virol., November 15, 2004; 78(22): 12386 - 12394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Llado, F. Tebar, M. Calvo, J. Moreto, A. Sorkin, and C. Enrich Protein KinaseC{delta}-Calmodulin Crosstalk Regulates Epidermal Growth Factor Receptor Exit from Early Endosomes Mol. Biol. Cell, November 1, 2004; 15(11): 4877 - 4891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Deb, C. M. Coticchia, and R. B. Dickson Calmodulin-mediated Activation of Akt Regulates Survival of c-Myc-overexpressing Mouse Mammary Carcinoma Cells J. Biol. Chem., September 10, 2004; 279(37): 38903 - 38911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Turner, A. K. Gelasco, and J. R. Raymond Calmodulin Interacts with the Third Intracellular Loop of the Serotonin 5-Hydroxytryptamine1A Receptor at Two Distinct Sites: PUTATIVE ROLE IN RECEPTOR PHOSPHORYLATION BY PROTEIN KINASE C J. Biol. Chem., April 23, 2004; 279(17): 17027 - 17037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vanoosthuyse, G. Tichtinsky, C. Dumas, T. Gaude, and J. M. Cock Interaction of Calmodulin, a Sorting Nexin and Kinase-Associated Protein Phosphatase with the Brassica oleracea S Locus Receptor Kinase Plant Physiology, October 1, 2003; 133(2): 919 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. PLANQUE, Y.-X. ZHOU, Y. NISHIYAMA, M. SINHA, M. O'CONNOR-MCCOURT, F. C. ARNETT, and S. PAUL Autoantibodies to the epidermal growth factor receptor in systemic sclerosis, lupus, and autoimmune mice FASEB J, February 1, 2003; 17(2): 136 - 143. [Abstract] [Full Text] [PDF]
|
|
