Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 1 April 2006, Vol. 107, No. 7, pp. 2745-2752.
Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-06-2547.

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-06-2547v1
107/7/2745    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maik-Rachline, G.
Right arrow Articles by Seger, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maik-Rachline, G.
Right arrow Articles by Seger, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Next Article next article arrow

Submitted June 28, 2005
Accepted November 21, 2005

Variable phosphorylation states of pigment epithelium-derived factor differentially regulate its function

Galia Maik-Rachline and Rony Seger*

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

* Corresponding author; email: rony.seger{at}weizmann.ac.il.

The pigment epithelium derived factor (PEDF) belongs to the family of non-inhibitory serpins. Although originally identified in the eye, PEDF is widely expressed in other body regions including the plasma. This factor can act either as a neurotrophic or as an antiangiogenic factor, and we previously showed that the two effects of PEDF are regulated through phosphorylation by PKA and CK2. Here we studied the interplay between the PKA and CK2 phosphorylation of PEDF, and found that a PEDF mutant mimicking the CK2-phosphorylated PEDF can not be phosphorylated by PKA, while the mutant mimicking the PKA-phosphorylated PEDF is a good CK2 substrate. Using triple mutants that mimic the PKA and CK2 phosphorylated and non-phosphorylated PEDF we found that PEDF can induce several distinct cellular activities dependent on its phosphorylation. The mutant mimicking the accumulative PKA plus CK2 phosphorylation exhibited the strongest antiangiogenic and neurotrophic activities, while the mutants mimicking the individual phosphorylation site mutants had either a reduced activity or only one of these activities. Thus, differential phosphorylation induces variable effects of PEDF, and therefore contributes to the complexity of PEDF action. It is likely that the triple phospho-mimetic mutant can be used to generate effective antiangiogenic or neurotrophic drugs.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020