Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin

The activity state of cofilin, which controls actin dynamics, is driven by a phosphorylation–dephosphorylation cycle. Phosphorylation of cofilin by LIM‐kinases results in its inactivation, a process supported by 14‐3‐3ζ and reversed by dephosphorylation by slingshot phosphatases. Here we report on a...

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Bibliographic Details
Published in:The EMBO journal Vol. 26; no. 19; pp. 4189 - 4202
Main Authors: Han, Li, Stope, Matthias B, de Jesús, Maider López, Oude Weernink, Paschal A, Urban, Martina, Wieland, Thomas, Rosskopf, Dieter, Mizuno, Kensaku, Jakobs, Karl H, Schmidt, Martina
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 03.10.2007
Nature Publishing Group UK
Springer Nature B.V
Nature Publishing Group
Subjects:
14-3-3
14-3-3 Proteins
Actins - genetics
Actins - metabolism
Cell Line
Cellular biology
cofilin
EMBO37
Gene Expression
Humans
Inactivation
Lim Kinases
LIM-kinase1
Molecular biology
Mutation
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
phospholipase D
Phospholipase D - genetics
Phospholipase D - metabolism
Phosphorylation
Protein Binding - physiology
Protein Kinases - genetics
Protein Kinases - metabolism
Protein Processing, Post-Translational - physiology
Receptors, Muscarinic - genetics
Receptors, Muscarinic - metabolism
Signal transduction
slingshot
phospholipase D
slingshot
cofilin
LIM‐kinase1
14‐3‐3
ISSN:0261-4189, 1460-2075
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Summary:The activity state of cofilin, which controls actin dynamics, is driven by a phosphorylation–dephosphorylation cycle. Phosphorylation of cofilin by LIM‐kinases results in its inactivation, a process supported by 14‐3‐3ζ and reversed by dephosphorylation by slingshot phosphatases. Here we report on a novel cellular function for the phosphorylation–dephosphorylation cycle of cofilin. We demonstrate that muscarinic receptor‐mediated stimulation of phospholipase D1 (PLD1) is controlled by LIM‐kinase, slingshot phosphatase as well as 14‐3‐3ζ, and requires phosphorylatable cofilin. Cofilin directly and specifically interacts with PLD1 and upon phosphorylation by LIM‐kinase1, stimulates PLD1 activity, an effect mimicked by phosphorylation‐mimic cofilin mutants. The interaction of cofilin with PLD1 is under receptor control and encompasses a PLD1‐specific fragment (aa 585–712). Expression of this fragment suppresses receptor‐induced cofilin–PLD1 interaction as well as PLD stimulation and actin stress fiber formation. These data indicate that till now designated inactive phospho‐cofilin exhibits an active cellular function, and suggest that phospho‐cofilin by its stimulatory effect on PLD1 may control a large variety of cellular functions.
Bibliography:ark:/67375/WNG-NNNFJZBP-D
ArticleID:EMBJ7601852
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These authors contributed equally to this work
Present address: Department of Infection Control, Chinese Military Institute of Disease Control & Prevention, Beijing 100071, China
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601852