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TPH1 is found in the periphery and pineal gland whereas TPH2 is expressed specifically in the CNS. Both TPH isoforms are known to be regulated by protein kinase\u2010dependent phosphorylation and the sites of modification of TPH1 by protein kinase A have been identified. While TPH2 is activated by calcium, calmodulin\u2010dependent protein kinase II (CaMKII), the sites at which this isoform is modified are not known. Treatment of wild\u2010type TPH2 with CaMKII followed by mass spectrometry analysis revealed that the enzyme was activated and phosphorylated at a single site, serine\u201019. Mutagenesis of serine\u201019 to alanine did not alter the catalytic function of TPH2 but this mutant enzyme was neither activated nor phosphorylated by CaMKII. A phosphopeptide bracketing phosphoserine\u201019 in TPH2 was used as an antigen to generate polyclonal antibodies against phosphoserine\u201019. The antibodies are highly specific for phosphoserine\u201019 in TPH2. The antibodies do not react with wild\u2010type TPH2 or TPH1 and they do not recognize phophoserine\u201058 or phosphoserine\u2010260 in TPH1. These results establish that activation of TPH2 by CaMKII is mediated by phosphorylation of serine\u201019 within the regulatory domain of the enzyme. Production of a specific antibody against the CaMKII phosphorylation site in TPH2 represents a valuable tool to advance the study of the mechanisms regulating the function of this important enzyme.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04855.x","type":"journal-article","created":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:18:42Z","timestamp":1188605922000},"page":"1567-1573","source":"Crossref","is-referenced-by-count":31,"title":["Phosphorylation and activation of tryptophan hydroxylase 2: identification of serine\u201019 as the substrate site for calcium, calmodulin\u2010dependent protein kinase II"],"prefix":"10.1111","volume":"103","author":[{"given":"Donald M.","family":"Kuhn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A.","family":"Sakowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Geddes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis","family":"Wilkerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Haycock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.11.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04213.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1016\/S0021-9258(18)67410-1","article-title":"Identification of four phosphorylation sites in the N\u2010terminal region of tyrosine hydroxylase","volume":"261","author":"Campbell D. 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