Interaction of Phosphorylated Tryptophan Hydroxylase with 14-3-3 Proteins

Banik, Utpal; Wang, Guoan; Wagner, Paul D.; Kaufman, Seymour

doi:10.1074/jbc.272.42.26219

Cited by 73 publications

(67 citation statements)

References 62 publications

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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

151

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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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

151

127

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“…The active site is located in a deep pocket formed by the loops of the (α/α) 6 barrel (shown in yellow in Fig. 5A) and two subdomains, I and II, which are inserted within the N-terminal half of the (α/α) 6 barrel (shown in cyan and green, respectively, in Fig. 5A), and contains a molecule of sucrose (SUC), which was present in the crystallization solution as an additive.…”

Section: Resultsmentioning

confidence: 99%

“…The structure of Nth1-CD consists of an (α/α) 6 barrel found in all enzymes belonging to the six-hairpin glycosidases superfamily of an α/α-toroidal fold. The active site is located in a deep pocket formed by the loops of the (α/α) 6 barrel (shown in yellow in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Mechanistically, 14-3-3 proteins act as allosteric regulators and/or molecular scaffolds that constrain the conformation of the binding partner; if the target protein is an enzyme, this can affect its catalytic activity. Many enzymes including c-Raf protein kinase (3), serotonin N-acetyltransferase (AANAT) (4), tyrosine and tryptophan hydroxylases (5,6), apoptosis signal-regulated protein kinase 1 (7), and Cdc25 phosphatases (8) have been shown to be regulated in such a manner. Nonetheless, the underlying molecular mechanisms are only partially identified, mainly as a result of the lack of structural data.…”

mentioning

confidence: 99%

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Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1

Alblova

Smidova

Dočekal

et al. 2017

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

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The 14-3-3 proteins, a family of highly conserved scaffolding proteins ubiquitously expressed in all eukaryotic cells, interact with and regulate the function of several hundreds of partner proteins. Yeast neutral trehalases (Nth), enzymes responsible for the hydrolysis of trehalose to glucose, compared with trehalases from other organisms, possess distinct structure and regulation involving phosphorylation at multiple sites followed by binding to the 14-3-3 protein. Here we report the crystal structures of yeast Nth1 and its complex with Bmh1 (yeast 14-3-3 isoform), which, together with mutational and fluorescence studies, indicate that the binding of Nth1 by 14-3-3 triggers Nth1’s activity by enabling the proper 3D configuration of Nth1’s catalytic and calcium-binding domains relative to each other, thus stabilizing the flexible part of the active site required for catalysis. The presented structure of the Bmh1:Nth1 complex highlights the ability of 14-3-3 to modulate the structure of a multidomain binding partner and to function as an allosteric effector. Furthermore, comparison of the Bmh1:Nth1 complex structure with those of 14-3-3:serotonin N-acetyltransferase and 14-3-3:heat shock protein beta-6 complexes revealed similarities in the 3D structures of bound partner proteins, suggesting the highly conserved nature of 14-3-3 affects the structures of many client proteins.

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“…26). Furthermore, 14-3-3 binding has been shown to protect phosphoserine residues from phosphatases and function as a scaffold to promote association with other proteins (27)(28)(29). Expression of 14-3-3 proteins in Xenopus oocytes activates the ERK pathway, and 14-3-3 proteins can potentiate ERK activation by KSR (22).…”

mentioning

confidence: 99%