Forkhead in rhabdomyosarcoma (FKHR) is a transcription factor that has been implicated in the control of gene expression by insulin, as well as the regulation of apoptosis by survival factors. These signals trigger the protein kinase B (PKB)-catalysed phosphorylation of FKHR at three residues (Thr24, Ser256 and Ser319) by a phosphoinositide 3-kinase-dependent pathway that results in the nuclear exit and inactivation of this transcription factor. Here, we have identified a conserved residue (Ser329) as a novel in vivo phosphorylation site on FKHR. Ser329 phosphorylation also decreases the ability of FKHR to stimulate gene transactivation and reduces the proportion of FKHR present in the nucleus. However, unlike the residues targetted by PKB, Ser329 is phosphorylated in unstimulated HEK-293cells, and phosphorylation is not increased by stimulation with insulin-like growth factor-1 or by transfection with 3-phosphoinositide-dependent protein kinase-1. We have also purified a protein kinase to near homogeneity from rabbit skeletal muscle that phosphorylates FKHR at Ser329 specifically and identified it as DYRK1A (dual-specificity tyrosine-phosphorylated and regulated kinase 1A). We find that FKHR and DYRK1A co-localize in discrete regions of the nucleus and can be co-immunoprecipitated from cell extracts. These experiments suggest that DYRK1A may phosphorylate FKHR at Ser329in vivo.
Skip Nav Destination
Article navigation
May 2001
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
April 24 2001
The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site
Yvonne L. WOODS;
Yvonne L. WOODS
*MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
Search for other works by this author on:
Graham RENA;
Graham RENA
*MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
Search for other works by this author on:
Nick MORRICE;
Nick MORRICE
*MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
Search for other works by this author on:
Andreas BARTHEL;
Andreas BARTHEL
†Institut fur Pharmakologie und Toxikologie, Medizinische Facultaet der RWTH Aaachen, Wendlingweg 2, D-52074, Aachen, Germany
Search for other works by this author on:
Walter BECKER;
Walter BECKER
†Institut fur Pharmakologie und Toxikologie, Medizinische Facultaet der RWTH Aaachen, Wendlingweg 2, D-52074, Aachen, Germany
Search for other works by this author on:
Shaodong GUO;
Shaodong GUO
‡University of Illinois College of Medicine at Chicago and Chicago Area Veterans Health Care System (West Side Division), Chicago, IL 60612, U.S.A.
Search for other works by this author on:
Terry G. UNTERMAN;
Terry G. UNTERMAN
‡University of Illinois College of Medicine at Chicago and Chicago Area Veterans Health Care System (West Side Division), Chicago, IL 60612, U.S.A.
Search for other works by this author on:
Philip COHEN
Philip COHEN
1
*MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
1To whom correspondence should be addressed (e-mail y.l.woods@dundee.ac.uk).
Search for other works by this author on:
Biochem J (2001) 355 (3): 597–607.
Article history
Received:
December 13 2000
Revision Received:
February 05 2001
Accepted:
February 27 2001
Citation
Yvonne L. WOODS, Graham RENA, Nick MORRICE, Andreas BARTHEL, Walter BECKER, Shaodong GUO, Terry G. UNTERMAN, Philip COHEN; The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site. Biochem J 1 May 2001; 355 (3): 597–607. doi: https://doi.org/10.1042/bj3550597
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.