Journalartikel

Jahr der Veröffentlichung: 2012

Seiten: 7265-7278

Zeitschrift: Journal of Biological Chemistry

Bandnummer: 287

Heftnummer: 10

eISSN: 1083-351X

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1074/jbc.M111.287599

Verlag: Elsevier

Abstract: 
Our previous work has shown that the membrane microdomain-associated flotillin proteins are potentially involved in epidermal growth factor (EGF) receptor signaling. Here we show that knockdown of flotillin-1/reggie-2 results in reduced EGF-induced phosphorylation of specific tyrosines in the EGF receptor (EGFR) and in inefficient activation of the downstream mitogen-activated protein (MAP) kinase and Akt signaling. Although flotillin-1 has been implicated in endocytosis, its depletion affects neither the endocytosis nor the ubiquitination of the EGFR. However, EGF-induced clustering of EGFR at the cell surface is altered in cells lacking flotillin-1. Furthermore, we show that flotillins form molecular complexes with EGFR in an EGF/EGFR kinase-independent manner. However, knockdown of flotillin-1 appears to affect the activation of the downstream MAP kinase signaling more directly. We here show that flotillin-1 forms a complex with CRAF, MEK1, ERK, and KSR1 (kinase suppressor of RAS) and that flotillin-1 knockdown leads to a direct inactivation of ERK1/2. Thus, flotillin-1 plays a direct role during both the early phase (activation of the receptor) and late (activation of MAP kinases) phase of growth factor signaling. Our results here unveil a novel role for flotillin-1 as a scaffolding factor in the regulation of classical MAP kinase signaling. Furthermore, our results imply that other receptor-tyrosine kinases may also rely on flotillin-1 upon activation, thus suggesting a general role for flotillin-1 as a novel factor in recepto-rtyrosine kinase/MAP kinase signaling.

Harvard-Zitierstil: Amaddii, M., Meister, M., Banning, A., Tomasovic, A., Mooz, J., Rajalingam, K., et al. (2012) Flotillin-1/Reggie-2 Protein Plays Dual Role in Activation of Receptor-tyrosine Kinase/Mitogen-activated Protein Kinase Signaling, Journal of Biological Chemistry, 287(10), pp. 7265-7278. https://doi.org/10.1074/jbc.M111.287599

APA-Zitierstil: Amaddii, M., Meister, M., Banning, A., Tomasovic, A., Mooz, J., Rajalingam, K., & Tikkanen, R. (2012). Flotillin-1/Reggie-2 Protein Plays Dual Role in Activation of Receptor-tyrosine Kinase/Mitogen-activated Protein Kinase Signaling. Journal of Biological Chemistry. 287(10), 7265-7278. https://doi.org/10.1074/jbc.M111.287599