Journal article
Phosphoinositides Are Essential Coactivators for p21-Activated Kinase 1
Molecular cell, v 40(3), pp 493-500
12 Nov 2010
PMID: 21070974
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Phospholipid-enriched membranes such as the plasma membrane can serve a 3 direct regulators of kinase signaling. Pak1 is involved in growth factor signaling at the plasma membrane, and its dysregulation is implicated in cancer. Pak1 adopts an autoinhibited conformation that is relieved upon binding to membrane-bound Rho GTPases Rac1 or Cdc42, but whether lipids also regulate Pak1 in vivo is unknown. We show here that phosphoinositides, particularly PIP2, potentiate Rho-GTPase-mediated Pak1 activity. A positively charged legion of Pak1 binds to phosphoinositide-containing membranes, and this interaction is essential for membrane recruitment and activation of Pak1 in response to extracellular signals. Our results highlight an active role for lipids as allosteric regulators of Pal(1 and suggest that Pak1 is a "coincidence detector" whose activation depends on GTPases present in phosphoinositide-rich membranes. These findings expand the role of phosphoinositides in kinase signaling and suggest how altered phosphoinositide metabolism may upregulate Pak1 activity in cancer cells.
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Details
- Title
- Phosphoinositides Are Essential Coactivators for p21-Activated Kinase 1
- Creators
- Todd I. Strochlic - Fox Chase Cancer CenterJulien Viaud - Fox Chase Cancer CenterUlrike E. E. Rennefahrt - Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USATheonie Anastassiadis - Fox Chase Cancer CenterJeffrey R. Peterson - Fox Chase Cancer Center
- Publication Details
- Molecular cell, v 40(3), pp 493-500
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- W.W. Smith Foundation P30CA006927 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RO1 GM083025; T32 CA009035; P30 CA006927 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM083025 / 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) American Cancer Society
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000284556300017
- Scopus ID
- 2-s2.0-78149451596
- Other Identifier
- 991020837829804721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology