Journal
CELLULAR SIGNALLING
Volume 21, Issue 6, Pages 847-858Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.01.031
Keywords
Annexins; EGF receptor; Ras/MAPK pathway; Endosomes; Actin
Categories
Funding
- National Health and Medical Research Council of Australia [510293, 510294]
- National Heart Foundation of Australia [G06S2559]
- Ministerio de Educacion y Ciencia, Spain [BFU2006-01151, V-2006-RET2008-0, PR-2006-0142]
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At the cell surface, activation of the epidermal growth factor (EGF) receptor triggers a complex network of signalling events that regulate a variety of cellular processes. For signal termination, the activated EGF receptor is internalised and targeted to lysosomes for degradation. Microdomain localization at the plasma membrane and endocytic transport of the EGFR is important for the formation of compartment-specific signalling complexes and is regulated by scaffolding and targeting proteins. This includes Ca2+-effector proteins, such as calmodulin and annexins (Anx), in particular AnxA1, AnxA2, AnxA6 and as shown recently, AnxA8. Given that these annexins show differences in their expression patterns, subcellular localization and mode of action, they are likely to differentially contribute and cooperate in the fine-tuning of EGFR activity. In support of this hypothesis, current literature suggests these annexins to be involved in different steps that control the endocytic transport and signalling of the EGF receptor. This review summarizes how the coordinated activity of AnxA1, AnxA2, AnxA6 and AnxA8 can contribute to regulate EGF receptor localization and activity. (C) 2009 Elsevier Inc. All rights reserved.
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