Journal article
PAK2 links cell survival to mechanotransduction and metabolism
The Journal of cell biology, Vol.218(6), pp.1958-1971
06/01/2019
DOI: 10.1083/jcb.201807152
PMCID: PMC6548143
PMID: 30940647
Abstract
Too little or too much force can trigger cell death, yet factors that ensure the survival of cells remain largely unknown. Here, we demonstrate that E-cadherin responds to force by recruiting and activating p21-activated protein kinase 2 (PAK2) to allow cells to stiffen, metabolize, and survive. Interestingly, PAK2 activation and its control of the apoptotic response are specific for the amplitude of force applied. Specifically, under low amplitudes of physiological force, PAK2 is protected from proteolysis, thereby ensuring cell survival. In contrast, under higher amplitudes of physiological force, PAK2 is left unprotected and stimulates apoptosis, an effect that is prevented by cleavage-resistant forms of the protein. Finally, we demonstrate that PAK2 protection is conferred by direct binding of AMPK. Thus, PAK2 mediates the survival of cells under force. These findings reveal an unexpected paradigm for how mechanotransduction, metabolism, and cell survival are linked.
Details
- Title: Subtitle
- PAK2 links cell survival to mechanotransduction and metabolism
- Creators
- Hannah K. Campbell - Roy J. and Lucille A. Carver College of MedicineAlicia M. Salvi - Roy J. and Lucille A. Carver College of MedicineTimothy O'Brien - Univ N Carolina, Dept Phys, Chapel Hill, NC 27515 USARichard Superfine - University of North Carolina at Chapel HillKris A. DeMali - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.218(6), pp.1958-1971
- DOI
- 10.1083/jcb.201807152
- PMID
- 30940647
- PMCID
- PMC6548143
- NLM abbreviation
- J Cell Biol
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Publisher
- Rockefeller Univ Press
- Number of pages
- 14
- Grant note
- 18PRE33960274 / American Heart Association P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32GM067795 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32 GM067795; P41-EB002025-34 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM112805 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P30CA086862 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P41EB002025 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
- Language
- English
- Date published
- 06/01/2019
- Academic Unit
- Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984288720002771
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