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Title: Calmodulin Regulates Intracellular Trafficking of Epidermal Growth Factor Receptor and the MAPK Signaling Pathway
Author: Tebar Ramon, Francesc
Vilallonga Smith, Príam de
Sorkina, Tatiana
Agell i Jané, Neus
Sorkin, Alexander
Enrich Bastús, Carles
Keywords: Calmodulina
Transducció de senyal cel·lular
Factor de creixement epidèrmic
Cellular signal transduction
Epidermal growth factor
Issue Date: 1-Mar-2002
Publisher: American Society for Cell Biology
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Molecular Biology of the Cell, 2002, vol. 13, núm. 6, p.2057-2068
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ISSN: 1059-1524
Appears in Collections:Articles publicats en revistes (Biomedicina)

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