Novel in vitro and in vivo phosphorylation sites on protein phosphatase 1 inhibitor CPI-17

CPI-17 is a protein phosphatase 1 (PP1) inhibitor that has been shown to act on the myosin light chain phosphatase. CPI-17 is phosphorylated on Thr-38 in vivo, thus enhancing its ability to inhibit PP1. Thr-38 has been shown to be the target of several protein kinases in vitro. Originally, the expre...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-03, Vol.302 (2), p.186-192
Main Authors: Dubois, Thierry, Howell, Steven, Zemlickova, Eva, Learmonth, Michele, Cronshaw, Andy, Aitken, Alastair
Format: Article
Language:English
Subjects:
Brain - metabolism
Brain Chemistry
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
CamKII
CKI
CPI-17
Cyclic AMP-Dependent Protein Kinases - metabolism
Humans
Muscle Proteins - isolation & purification
Muscle Proteins - metabolism
Muscle Proteins - pharmacology
Phosphatase inhibitor
Phosphoprotein Phosphatases - antagonists & inhibitors
Phosphoprotein Phosphatases - metabolism
Phosphoproteins - isolation & purification
Phosphoproteins - metabolism
Phosphoproteins - pharmacology
Phosphorylation
PKA
Protein Phosphatase 1
Serine - metabolism
Threonine - metabolism
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Summary:CPI-17 is a protein phosphatase 1 (PP1) inhibitor that has been shown to act on the myosin light chain phosphatase. CPI-17 is phosphorylated on Thr-38 in vivo, thus enhancing its ability to inhibit PP1. Thr-38 has been shown to be the target of several protein kinases in vitro. Originally, the expression of CPI-17 was proposed to be smooth muscle specific. However, it has recently been found in platelets and we show in this report that it is endogenously phosphorylated in brain on Ser-128 in a domain unique to CPI-17. Ser-128 is within a consensus phosphorylation site for protein kinase A (PKA) and calcium calmodulin kinase II. However, these two kinases do not phosphorylate Ser-128 in vitro but phosphorylate Ser-130 and Thr-38, respectively. The kinase responsible for Ser-128 phosphorylation remains to be identified. CPI-17 has strong sequence similarity with PHI-1 (which is also a phosphatase inhibitor) and LimK-2 kinase. The novel in vivo and in vitro phosphorylation sites (serines 128 and 130) are in a region/domain unique to CPI-17, suggesting a specific interaction domain that is regulated by phosphorylation.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)00130-X