| Flotillin-1/reggie-2 protein plays dual role in activation of receptor-tyrosine kinase/mitogen-activated protein kinase signaling. | |
| | |
MedLine Citation:
|
PMID: 22232557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 receptor-tyrosine kinase/MAP kinase signaling. |
| | |
Authors:
|
Monia Amaddii; Melanie Meister; Antje Banning; Ana Tomasovic; Juliane Mooz; Krishnaraj Rajalingam; Ritva Tikkanen |
Related Documents
:
|
20643547 - 4-anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated p... 20832307 - Pyrazolobenzodiazepines: part i. synthesis and sar of a potent class of kinase inhibitors. 20045647 - Synthesis and optimization of thiadiazole derivatives as a novel class of substrate com... 10629537 - Synthesis and biological evaluation of a targeted library of protein phosphatase inhibi... 21825007 - Targeting the microtubular network as a new anti-myeloma strategy. 9649427 - Fizzy is required for activation of the apc/cyclosome in xenopus egg extracts. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-01-09 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-03-05 Completed Date: 2012-04-24 Revised Date: 2013-04-15 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 7265-78 Citation Subset: IM |
Affiliation:
|
From the Institute of Biochemistry, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Enzyme Activation
/
physiology Epidermal Growth Factor / genetics, metabolism Gene Knockdown Techniques HeLa Cells Humans MAP Kinase Kinase 1 / genetics, metabolism MAP Kinase Signaling System / physiology* Membrane Proteins / genetics, metabolism* Mitogen-Activated Protein Kinase 1 / genetics, metabolism Mitogen-Activated Protein Kinase 3 / genetics, metabolism Multiprotein Complexes / genetics, metabolism* Protein Kinases / genetics, metabolism Proto-Oncogene Proteins c-akt / genetics, metabolism Receptor, Epidermal Growth Factor / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Membrane Proteins; 0/Multiprotein Complexes; 0/flotillins; 62229-50-9/Epidermal Growth Factor; EC 2.7.-/Protein Kinases; EC 2.7.1.-/KSR-1 protein kinase; EC 2.7.1.-/MAP2K1 protein, human; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.12.2/MAP Kinase Kinase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Protein kinase C (PKC)?-mediated G?q stimulation of ERK5 protein pathway in cardiomyocytes and cardi...
Next Document: Conserved Ser/Arg-rich motif in PPZ orthologs from fungi is important for its role in cation toleran...