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Cyclin‐dependent kinase 11 p110 and casein kinase 2 (CK2) inhibit the interaction between tyrosine hydroxylase and 14‐3‐3
Author(s) -
Sachs Nancy A.,
Vaillancourt Richard R.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02119.x
Subject(s) - casein kinase 1 , phosphorylation , casein kinase 2 , casein kinase 2, alpha 1 , serine , phosphoserine , biochemistry , kinase , biology , dephosphorylation , phosphopeptide , alanine , tyrosine hydroxylase , cyclin dependent kinase 2 , protein kinase a , microbiology and biotechnology , enzyme , amino acid , phosphatase
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.