Demonstration of the Phosphorylation-Dependent Interaction of Tryptophan Hydroxylase with the 14-3-3 Protein

Furukawa, Yoshitaka; Ikuta, Nilo; Omata, Saburo; Yamauchi, Takashi; Isobe, Toshiaki; Ichimura, Tsuyoshi

doi:10.1006/bbrc.1993.1796

Cited by 96 publications

(63 citation statements)

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“…As CaMPKII phosphorylation has been demonstrated to increase TPH activity, it is directly relevant to understanding the regulation of TPH activity. Like PKA, CaMPKII phosphorylation-dependent activation of TPH appears to require the activator protein 14-3-3 (Yamauchi et al, 1981;Ichimura et al, 1987Ichimura et al, , 1988Ichimura et al, , 1995Makita et al, 1990;Isobe et al, 1991;Furukawa et al, 1993). However, PKA or CaMPKII phosphorylation-dependent activation of TPH has not been universally observed even in the presence of 14-3-3 Johansen et al, 1995;and this report).…”

Section: Discussionmentioning

confidence: 58%

“…It has been suggested that 14-3-3, a ubiquitous cytosolic protein, serves as a specific activator of phosphorylated TH and TPH (Yamauchi et al, 1981;Ichimura et al, 1987Ichimura et al, , 1988Ichimura et al, , 1995Isobe et al, 1991). Moreover, the 14-3-3 interaction appears to occur after the phosphorylation event and may act to stabilize the phosphorylated enzyme (Furukawa et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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Amino‐Terminal Analysis of Tryptophan Hydroxylase: Protein Kinase Phosphorylation Occurs at Serine‐58

Kumer

Mockus

Rucker

et al. 1997

Journal of Neurochemistry

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Tryptophan hydroxylase (TPH) catalyzes the rate-limiting and committed step in serotonin biosynthesis. Within this enzyme, two distinct domains have been hypothesized to exist, an amino-terminal regulatory domain and a carboxyl-terminal catalytic domain. In the present experiments, the functional boundary between the putative domains was defined using deletion mutagenesis. A full-length cDNA clone for rabbit TPH was engineered for expression in bacteria. Five amino-terminal deletions were constructed using PCR, i.e., Nz~50, Nz~60, N~90,Nz~106, and NL~~116 (referring to the number of amino acids deleted from the amino terminus). Enzymatic activity was determined for each mutant after expression in bacteria. Whereas deletion of 116 amino acids (Nz~116) abolished enzyme activity, all of the other amino-terminal deletions exhibited increased specific activity relative to the recombinant wild-type TPH. The ability of the cyclic AMP-dependent protein kinase (PKA) to phosphorylate members of the deletion series was also examined. Deletion of the first 60 amino-terminal residues abolished the ability of the enzymeto serve as a substrate for PKA, yet the native and N~50enzymes were phosphotylated. Moreover, a serine-58 point mutant (S58A) was not phosphorylated by PKA. In conclusion, the first 106 amino acids comprise a regulatory domain that is phosphorylated by PKA at serine-58. In addition, the boundary between regulatory and catalytic domains is analogous to the domain structure observed for the related enzyme tyrosine hydroxylase.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Amino‐Terminal Analysis of Tryptophan Hydroxylase: Protein Kinase Phosphorylation Occurs at Serine‐58

Kumer

Mockus

Rucker

et al. 1997

Journal of Neurochemistry

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“…Many interactions with 14-3-3 are mediated by target phosphorylation (25,26,41,42). To determine whether the ASK1-14-3-3 interaction is phosphorylation-dependent, we incubated 35 Slabeled ASK1 with potato acid phosphatase for various lengths of time before adding immobilized 14-3-3 protein.…”

Section: Resultsmentioning

confidence: 99%

Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins

Zhang

Chen

1999

Proc. Natl. Acad. Sci. U.S.A.

339

296

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Apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component of a signaling pathway induced by many death stimuli, including tumor necrosis factor ␣, Fas, and the anticancer drugs cisplatin and paclitaxel. Here we report that ASK1 proapoptotic activity is antagonized by association with 14-3-3 proteins. We found that ASK1 specifically bound 14-3-3 proteins via a site involving Ser-967 of ASK1. Interestingly, overexpression of 14-3-3 in HeLa cells blocked ASK1-induced apoptosis whereas disruption of the ASK1/14-3-3 interaction dramatically accelerated ASK1-induced cell death. Targeting of ASK1 by a 14-3-3-mediated survival pathway may provide a novel mechanism for the suppression of apoptosis.

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“…In this study, we extended our investigation to examine post-translational modification of TPH protein (Furukawa et al, 1993;Ichimura et al, 1995;Banik et al, 1997;Kuhn et al, 1997), corroborate our [ 3 H]citalopram-binding results with a direct measurement of SERT protein, and examine the expression of the two degradative proteins, MAO-A and MAO-B. We also compared a longer treatment period to our standard 1 mo replacement regimen and determined the effect of a selective estrogen receptor (ER) Figure 5 Histograms illustrating the mean7SEM (n ¼ 4 per group) of TPH protein and phosphorylated TPH optical density in groups of monkeys that were spayed, treated with estrogen for one mo (E1), or treated with estrogen for 5 mo (E5).…”

Section: Discussionmentioning

confidence: 99%

Effects of Ovarian Steroids and Raloxifene on Proteins that Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques

Smith

Henderson

Abell

et al. 2004

Neuropsychopharmacol

152

127

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In the monkey dorsal raphe, we reported that 1-month (mo) of estrogen replacement, with or without progesterone supplementation for 14 days, significantly increased tryptophan hydroxylase-1 (TPH-1) mRNA; decreased serotonin reuptake transporter (SERT) mRNA and decreased monoamine oxidase (MAO)-A mRNA, but had no effect on MAO-B mRNA. Here, we questioned what effect would 1 or 5 mo of ovarian hormones or the selective estrogen receptor modulator (SERM), raloxifene, have on TPH protein and phosphorylation, and on protein expression of SERT, MAO-A or MAO-B? Raloxifene antagonizes estrogen in breast or uterus, but estrogen-like activities in the brain have been reported. Cytoplasmic and membrane extracts of the dorsal raphe region were processed for Western blotting. TPH, phosphoserine, SERT, MAO-A, and MAO-B were detected with specific antibodies. The optical densities of the signals were measured with NIH image and analyzed by ANOVA. Both 1 and 5 mo of estrogen, with or without progesterone, and 5 mo of raloxifene significantly increased TPH protein. Administration for 5 mo of estrogen plus progesterone and raloxifene also increased TPH phosphorylation. Estrogen, with or without progesterone, for 1 mo had no effect on SERT protein. However, 5 mo of estrogen and 5 mo of raloxifene increased SERT protein. Estrogen alone or combined with progesterone for 1 mo caused a significant reduction in MAO-A. Yet, after 5 mo of the same treatments, MAO-A was not different from spayed controls. Estrogen alone had no effect on MAO-B. However, the addition of progesterone significantly increased MAO-B. Raloxifene for 5 mo had no effect on MAO-A or MAO-B. Thus, to various extents, estrogen, progesterone, and raloxifene may increase serotonin production and transport. The expression of the degradative enzymes suggests a complex combination of gene transcription, post-transcriptional processing, and substrate feedback mechanisms.

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Demonstration of the Phosphorylation-Dependent Interaction of Tryptophan Hydroxylase with the 14-3-3 Protein

Cited by 96 publications

References 0 publications

Amino‐Terminal Analysis of Tryptophan Hydroxylase: Protein Kinase Phosphorylation Occurs at Serine‐58

Amino‐Terminal Analysis of Tryptophan Hydroxylase: Protein Kinase Phosphorylation Occurs at Serine‐58

Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins

Effects of Ovarian Steroids and Raloxifene on Proteins that Synthesize, Transport, and Degrade Serotonin in the Raphe Region of Macaques

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