Cyclin‐dependent kinase 11 p110 and casein kinase 2 (CK2) inhibit the interaction between tyrosine hydroxylase and 14‐3‐3
Abstract Tyrosine hydroxylase (TH) is regulated by the reversible phosphorylation of serines 8, 19, 31 and 40. Upon initiation of this study, serine 19 was unique due to its requirement of 14‐3‐3 binding after phosphorylation for optimal enzyme activity, although it has been more recently demonstrat...
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Published in | Journal of neurochemistry Vol. 88; no. 1; pp. 51 - 62 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
01.01.2004
|
Online Access | Get full text |
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Summary: | Abstract
Tyrosine hydroxylase (TH) is regulated by the reversible phosphorylation of serines 8, 19, 31 and 40. Upon initiation of this study, serine 19 was unique due to its requirement of 14‐3‐3 binding after phosphorylation for optimal enzyme activity, although it has been more recently demonstrated that phosphorylated serine 40 also binds 14‐3‐3. To identify proteins that interact with TH following phosphorylation of serine 19, this amino acid was mutated to alanine and THS19A was used as bait in a yeast two‐hybrid system. From this, mouse‐derived cyclin‐dependent kinase 11 (CDK11)
p110
was identified as an interacting partner with THS19A. The interaction was confirmed using human CDK11
p110
cDNA in a mammalian system. Previous research has demonstrated that casein kinase 2 (CK2) interacts with CDK11
p110
, and both were observed to phosphorylate TH
in vitro
. In addition, CDK11
p110
overexpression was observed to inhibit the interaction between TH and 14‐3‐3. A mechanism contributing to disruption of the interaction between TH and 14‐3‐3 may be due to CK2 phosphorylation of specific 14‐3‐3 isoforms, i.e. 14‐3‐3 τ. Collectively, these results imply that CDK11
p110
and CK2 negatively regulate TH catecholamine biosynthetic activity since phosphoserine 19 of TH requires 14‐3‐3 binding for optimal enzyme activity and a decreased rate of dephosphorylation. |
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ISSN: | 0022-3042 1471-4159 |
DOI: | 10.1046/j.1471-4159.2003.02119.x |