Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 5, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2017.00034
Keywords
tetraspanins; signal transduction; tetraspanin-enriched microdomains; adhesion-mediated signaling; receptor-mediated signal transduction
Categories
Funding
- F31 Fellowship from the National Heart, Lung, and Blood Institute [F31HL124977]
- American Heart Association [13SDG14630080]
- NIH investigator grant [RO1HL122483-01]
- NIH [P50 GM085273]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL122483, F31HL124977] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM085273] Funding Source: NIH RePORTER
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Tetraspanins are molecular scaffolds that distribute proteins into highly organized microdomains consisting of adhesion, signaling, and adaptor proteins. Many reports have identified interactions between tetraspanins and signaling molecules, finding unique downstream cellular consequences. In this review, we will explore these interactions as well as the specific cellular responses to signal activation, focusing on tetraspanin regulation of adhesion-mediated (integrins/FAK), receptor-mediated (EGFR, TNF-alpha, c-Met, c-Kit), and intracellular signaling (PKC, PI4K, beta-catenin). Additionally, we will summarize our current understanding for how tetraspanin post-translational modifications (palmitoylation, N-linked glycosylation, and ubiquitination) can regulate signal propagation. Many of the studies outlined in this review suggest that tetraspanins offer a potential therapeutic target to modulate aberrant signal transduction pathways that directly impact a host of cellular behaviors and disease states.
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