Document Detail

Protein phosphatase-2A associates with and dephosphorylates keratin 8 after hyposmotic stress in a site- and cell-specific manner.
MedLine Citation:
PMID:  16554440     Owner:  NLM     Status:  MEDLINE    
Keratins 8 and 18 (K8 and K18) are regulated by site-specific phosphorylation in response to multiple stresses. We examined the effect and regulation of hyposmotic stress on keratin phosphorylation. K8 phospho-Ser431 (Ser431-P) becomes dephosphorylated in HT29 cells, but hyperphosphorylated on other K8 but not K18 sites in HRT18 and Caco2 cells and in normal human colonic ex vivo cultures. Hyposmosis-induced dephosphorylation involves K8 but not K18, K19 or K20, occurs preferentially in mitotically active cells, and peaks by 6-8 hours then returns to baseline by 12-16 hours. By contrast, hyperosmosis causes K8 Ser431 hyperphosphorylation in all tested cell lines. Hyposmosis-induced dephosphorylation of K8 Ser431-P is inhibited by okadaic acid but not by tautomycin or cyclosporine. The PP2A catalytic subunit co-immunoprecipitated with K8 and K18 after hyposmotic stress in HT29 cells, but not in HRT18 or Caco2 cells where K8 Ser431 becomes hyperphosphorylated. K8 Ser431-P dephosphorylation after hyposmosis was independent of PP2A levels but correlated with increased PP2A activity towards K8 Ser431-P. Therefore, hyposmotic stress alters K8 phosphorylation in a cell-dependent manner, and renders K8 Ser431-P a physiologic substrate for PP2A in HT29 cells as a result of PP2A activation and the physical association with K8 and K18. The divergent hyposmosis versus hyperosmosis K8 Ser431 phosphorylation changes in HT29 cells suggest that there are unique signaling responses to osmotic stress.
Guo-Zhong Tao; Diana M Toivola; Qin Zhou; Pavel Strnad; Baohui Xu; Sara A Michie; M Bishr Omary
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of cell science     Volume:  119     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-23     Completed Date:  2006-06-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1425-32     Citation Subset:  IM    
Department of Medicine, Palo Alto VA Medical Center, 3801 Miranda Avenue, Mail Code 154J, Palo Alto, CA 94304, USA.
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MeSH Terms
Caco-2 Cells
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique, Indirect
Fluorescent Dyes
HT29 Cells
Hypotonic Solutions
Keratins / chemistry*,  metabolism*
Microscopy, Confocal
Models, Biological
Okadaic Acid / pharmacology
Phosphoprotein Phosphatases / metabolism*
Protein Phosphatase 2
Serine / metabolism*
Stress, Physiological / metabolism*
Substrate Specificity / drug effects
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fluorescent Dyes; 0/Hypotonic Solutions; 0/Xanthenes; 3326-32-7/Fluorescein-5-isothiocyanate; 56-45-1/Serine; 68238-35-7/Keratins; 78111-17-8/Okadaic Acid; 82354-19-6/Texas red; EC Phosphatases; EC Phosphatase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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