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Article: TRP proteins and cancer.

Bödding, Matthias

2007 Volume 19, Issue 3, Page(s) 617–624

Abstract: Cancer is the second most common cause of death in western countries. It is therefore of fundamental importance to improve the treatment of patients with malignant tumors. This goal can only be achieved if we get closer insight in the various mechanisms ... ...

Abstract	Cancer is the second most common cause of death in western countries. It is therefore of fundamental importance to improve the treatment of patients with malignant tumors. This goal can only be achieved if we get closer insight in the various mechanisms leading to tumor formation. Significant progress in the understanding of carcinogenesis has been made during the last couple of years. Ion channels contribute to the regulation of cell proliferation which has initially been shown for K+ channels. Meanwhile, other ion channels such as Cl-, Na+ and Ca2+ channels seem to influence cellular function like growth, migration and invasion. In addition, cation channels of the transient receptor potential (TRP) superfamily are implicated in cancer formation. Most recent data concerning TRP vanilloid (TRPV) type 6, TRP melastatin (TRPM) type 1 and 8 channels and their relevance for common human cancer types will be highlighted in this review. Furthermore, TRP channel structure and function will be discussed in the light of their possible importance as prognostic markers and targets for drug discovery.
MeSH term(s)	Calcium Channels/genetics ; Calcium Channels/physiology ; Forecasting ; Humans ; Neoplasms/etiology ; TRPM Cation Channels/genetics ; TRPM Cation Channels/physiology ; TRPV Cation Channels/genetics ; TRPV Cation Channels/physiology
Chemical Substances	Calcium Channels ; TRPM Cation Channels ; TRPM1 protein, human ; TRPM8 protein, human ; TRPV Cation Channels ; TRPV5 protein, human ; TRPV6 protein, human
Language	English
Publishing date	2007-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1002702-6
ISSN	0898-6568
ISSN	0898-6568
DOI	10.1016/j.cellsig.2006.08.012
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Article ; Online: Metabolism of (R)-Praziquantel versus the Activation of a Parasite Transient Receptor Potential Melastatin Ion Channel.

Friedrich, Lukas / Park, Sang-Kyu / Ballard, Peter / Ho Baeurle, Tobias Hyun / Maillard, David / Bödding, Matthias / Keiser, Jennifer / Marchant, Jonathan S / Spangenberg, Thomas

ChemMedChem

2023 Volume 18, Issue 18, Page(s) e202300140

Abstract: Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin ( ... ...

Abstract	Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPM
MeSH term(s)	Humans ; Animals ; Praziquantel/pharmacology ; Praziquantel/chemistry ; Parasites ; Transient Receptor Potential Channels ; TRPM Cation Channels ; Anthelmintics/pharmacology ; Anthelmintics/therapeutic use ; Schistosoma mansoni
Chemical Substances	Praziquantel (6490C9U457) ; Transient Receptor Potential Channels ; TRPM Cation Channels ; Anthelmintics
Language	English
Publishing date	2023-06-15
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202300140
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Article ; Online: A First-in-human, Dose-escalation Study of the Methionine Aminopeptidase 2 Inhibitor M8891 in Patients with Advanced Solid Tumors.

Carducci, Michael A / Wang, Ding / Habermehl, Christina / Bödding, Matthias / Rohdich, Felix / Lignet, Floriane / Duecker, Klaus / Karpenko, Oleksandr / Pudelko, Linda / Gimmi, Claude / LoRusso, Patricia

Cancer research communications

2023 Volume 3, Issue 8, Page(s) 1638–1647

Abstract: Methionine aminopeptidase 2 (MetAP2) is essential to endothelial cell growth and proliferation during tumor angiogenesis. M8891 is a novel orally bioavailable, potent, selective, reversible MetAP2 inhibitor with antiangiogenic and antitumor activity in ... ...

Abstract	Methionine aminopeptidase 2 (MetAP2) is essential to endothelial cell growth and proliferation during tumor angiogenesis. M8891 is a novel orally bioavailable, potent, selective, reversible MetAP2 inhibitor with antiangiogenic and antitumor activity in preclinical studies. The safety, tolerability, pharmacokinetics, and pharmacodynamics of M8891 monotherapy were assessed in a phase I, first-in-human, multicenter, open-label, single-arm, dose-escalation study (NCT03138538). Patients with advanced solid tumors received 7-80 mg M8891 once daily in 21-day cycles. The primary endpoint was dose-limiting toxicity (DLT) during cycle 1, with the aim to determine the maximum tolerated dose (MTD). Twenty-seven patients were enrolled across six dose levels. Two DLTs (platelet count decrease) were reported, one each at 60 and 80 mg/once daily M8891, resolving after treatment discontinuation. MTD was not determined. The most common treatment-emergent adverse event was platelet count decrease. M8891 plasma concentration showed dose-linear increase up to 35 mg and low-to-moderate variability; dose-dependent tumor accumulation of methionylated elongation factor 1α, a MetAP2 substrate, was observed, demonstrating MetAP2 inhibition. Pharmacokinetic/pharmacodynamic response data showed that preclinically defined target levels required for Significance: M8891 represents a novel class of reversible MetAP2 inhibitors and has demonstrated preclinical antitumor activity. This dose-escalation study assessed M8891 treatment for patients with advanced solid tumors. M8891 demonstrated favorable pharmacokinetics, tumoral target engagement, and a manageable safety profile, and thus represents a novel antitumor strategy warranting further clinical studies.
MeSH term(s)	Humans ; Neoplasms/drug therapy ; Aminopeptidases ; Metalloendopeptidases ; Angiogenesis Inhibitors/adverse effects ; Enzyme Inhibitors
Chemical Substances	methionine aminopeptidase 2 (EC 3.4.11.18) ; Aminopeptidases (EC 3.4.11.-) ; Metalloendopeptidases (EC 3.4.24.-) ; Angiogenesis Inhibitors ; Enzyme Inhibitors
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Clinical Trial, Phase I ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-23-0048
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Article: Voltage-dependent changes of TRPV6-mediated Ca2+ currents.

Bödding, Matthias

The Journal of biological chemistry

2004 Volume 280, Issue 8, Page(s) 7022–7029

Abstract: The physiological role and activation mechanism for most proteins of the transient receptor potential (TRP) family are unknown. This is also the case for the highly Ca(2+) selective transient receptor potential vanilloid type 6 (TRPV6) channel. Patch ... ...

Abstract	The physiological role and activation mechanism for most proteins of the transient receptor potential (TRP) family are unknown. This is also the case for the highly Ca(2+) selective transient receptor potential vanilloid type 6 (TRPV6) channel. Patch clamp experiments were performed on transiently transfected human embryonic kidney (HEK) cells to address this issue. Currents were recorded under various conditions of intracellular Ca(2+) buffering and monitored at the same voltage throughout. No TRPV6-mediated Ca(2+) entry was detected under in vivo Ca(2+) buffering conditions at a slightly negative holding potential; however, moderate depolarization resulted in current activation. Very similar results were obtained with different Ca(2+) chelators, either EGTA or BAPTA dialyzing the cell. TRPV6 channel activity showed a negative correlation with the intracellular free Ca(2+) concentration ([Ca(2+)](i)) and was modulated by the membrane potential: Hyperpolarization decreases and depolarization increases TRPV6-mediated currents. Monovalent ions permeated TRPV6 channels in the absence of extracellular divalent cations. These currents were resistant to changes in the holding potential while the negative correlation to the [Ca(2+)](i) was conserved, indicating that the voltage-dependent current changes depend on blocking and unblocking the charge carrier Ca(2+) within the pore. In summary, these results suggest that the voltage dependence of TRPV6-mediated Ca(2+) influx is of physiological importance since it occurs at cytosolic Ca(2+) buffering and takes place within a physiologically relevant membrane potential range.
MeSH term(s)	Biological Transport ; Calcium/metabolism ; Calcium Channels/physiology ; Cell Line ; Egtazic Acid/pharmacology ; Electrophysiology ; Humans ; Membrane Potentials/physiology ; Patch-Clamp Techniques ; TRPV Cation Channels ; Transfection
Chemical Substances	Calcium Channels ; TRPV Cation Channels ; TRPV6 channel ; Egtazic Acid (526U7A2651) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2004-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M410184200
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Book ; Online ; Thesis: Expression, calciumfluorimetrische und elektrophysiologische Untersuchung von TRPC6 in chromaffinen Nebennierenzellen von Mäusen

Büttner, Bastian Raphael [Verfasser] / Bödding, Matthias [Akademischer Betreuer]

2018

Author's details	Bastian Raphael Büttner ; Betreuer: Matthias Bödding
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	German
Publisher	Saarländische Universitäts- und Landesbibliothek
Publishing place	Saarbrücken
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.

N'Goran, Eliézer K / Odiere, Maurice R / Assandé Aka, Ronald / Ouattara, Mamadou / Aka, N A David / Ogutu, Bernhards / Rawago, Fredrick / Bagchus, Wilhelmina M / Bödding, Matthias / Kourany-Lefoll, Elly / Tappert, Aliona / Yin, Xiaoyan / Bezuidenhout, Deon / Badenhorst, Henk / Huber, Eric / Dälken, Benjamin / Haj-Ali Saflo, Okba

The Lancet. Infectious diseases

2023 Volume 23, Issue 7, Page(s) 867–876

Abstract: Background: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, ... ...

Abstract	Background: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. Methods: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. Findings: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). Interpretation: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. Funding: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
MeSH term(s)	Animals ; Child, Preschool ; Male ; Female ; Humans ; Praziquantel/adverse effects ; Cote d'Ivoire ; Kenya ; Schistosomiasis mansoni/drug therapy ; Schistosomiasis mansoni/diagnosis ; Schistosomiasis mansoni/prevention & control ; Anthelmintics/adverse effects ; Schistosoma mansoni ; Schistosomiasis/drug therapy
Chemical Substances	Praziquantel (6490C9U457) ; Anthelmintics
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00048-8
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Article ; Online: Causal chemoprophylactic activity of cabamiquine against Plasmodium falciparum in a controlled human malaria infection: a randomised, double-blind, placebo-controlled study in the Netherlands.

van der Plas, Johan L / Kuiper, Vincent P / Bagchus, Wilhelmina M / Bödding, Matthias / Yalkinoglu, Özkan / Tappert, Aliona / Seitzinger, Andrea / Spangenberg, Thomas / Bezuidenhout, Deon / Wilkins, Justin / Oeuvray, Claude / Dhingra, Satish K / Thathy, Vandana / Fidock, David A / Smidt, Lisanne C A / Roozen, Geert V T / Koopman, Jan Pieter R / Lamers, Olivia A C / Sijtsma, Jeroen /

van Schuijlenburg, Roos / Wessels, Els / Meij, Pauline / Kamerling, Ingrid M C / Roestenberg, Meta / Khandelwal, Akash

The Lancet. Infectious diseases

2023 Volume 23, Issue 10, Page(s) 1164–1174

Abstract: Background: Cabamiquine is a novel antimalarial that inhibits Plasmodium falciparum translation elongation factor 2. We investigated the causal chemoprophylactic activity and dose-exposure-response relationship of single oral doses of cabamiquine ... ...

Abstract	Background: Cabamiquine is a novel antimalarial that inhibits Plasmodium falciparum translation elongation factor 2. We investigated the causal chemoprophylactic activity and dose-exposure-response relationship of single oral doses of cabamiquine following the direct venous inoculation (DVI) of P falciparum sporozoites in malaria-naive, healthy volunteers. Methods: This was a phase 1b, randomised, double-blind, placebo-controlled, adaptive, dose-finding, single-centre study performed in Leiden, Netherlands. Malaria-naive, healthy adults aged 18-45 years were divided into five cohorts and randomly assigned (3:1) to receive cabamiquine or placebo. Randomisation was done by an independent statistician using codes in a permuted block schedule with a block size of four. Participants, investigators, and study personnel were masked to treatment allocation. A single, oral dose regimen of cabamiquine (200, 100, 80, 60, or 30 mg) or matching placebo was administered either at 2 h (early liver-stage) or 96 h (late liver-stage) after DVI. The primary endpoints based on a per-protocol analysis set were the number of participants who developed parasitaemia within 28 days of DVI, time to parasitaemia, number of participants with documented parasite blood-stage growth, clinical symptoms of malaria, and exposure-efficacy modelling. The impact of cabamiquine on liver stages was evaluated indirectly by the appearance of parasitaemia in the blood. The Clopper-Pearson CI (nominal 95%) was used to express the protection rate. The secondary outcomes were safety and tolerability, assessed in those who had received DVI and were administered one dose of the study intervention. The trial was prospectively registered on ClinicalTrials.gov (NCT04250363). Findings: Between Feb 17, 2020 and April 29, 2021, 39 healthy participants were enrolled (early liver-stage: 30 mg [n=3], 60 mg [n=6], 80 mg [n=6], 100 mg [n=3], 200 mg [n=3], pooled placebo [n=6]; late liver-stage: 60 mg [n=3], 100 mg [n=3], 200 mg [n=3], pooled placebo [n=3]). A dose-dependent causal chemoprophylactic effect was observed, with four (67%) of six participants in the 60 mg, five (83%) of six participants in the 80 mg, and all three participants in the 100 and 200 mg cabamiquine dose groups protected from parasitaemia up to study day 28, whereas all participants in the pooled placebo and 30 mg cabamiquine dose group developed parasitaemia. A single, oral dose of 100 mg cabamiquine or higher provided 100% protection against parasitaemia when administered during early or late liver-stage malaria. The median time to parasitaemia in those with early liver-stage malaria was prolonged to 15, 22, and 24 days for the 30, 60, and 80 mg dose of cabamiquine, respectively, compared with 10 days for the pooled placebo. All participants with positive parasitaemia showed documented blood-stage parasite growth, apart from one participant in the pooled placebo group and one participant in the 30 mg cabamiquine group. Most participants did not exhibit any malaria symptoms in both the early and late liver-stage groups, and those reported were mild in severity. A positive dose-exposure-efficacy relationship was established across exposure metrics. The median maximum concentration time was 1-6 h, with a secondary peak observed between 6 h and 12 h in all cabamiquine dose groups (early liver-stage). All cabamiquine doses were safe and well tolerated. Overall, 26 (96%) of 27 participants in the early liver-stage group and ten (83·3%) of 12 participants in the late liver-stage group reported at least one treatment-emergent adverse event (TEAE) with cabamiquine or placebo. Most TEAEs were of mild severity, transient, and resolved without sequelae. The most frequently reported cabamiquine-related TEAE was headache. No dose-related trends were observed in the incidence, severity, or causality of TEAEs. Interpretation: The results from this study show that cabamiquine has a dose-dependent causal chemoprophylactic activity. Together with previously demonstrated activity against the blood stages combined with a half-life of more than 150 h, these results indicate that cabamiquine could be developed as a single-dose monthly regimen for malaria prevention. Funding: The healthcare business of Merck KGaA, Darmstadt, Germany.
MeSH term(s)	Adult ; Humans ; Plasmodium falciparum ; Netherlands ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/prevention & control ; Malaria, Falciparum/parasitology ; Antimalarials ; Healthy Volunteers ; Double-Blind Method
Chemical Substances	Antimalarials
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00212-8
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Book ; Thesis: Beeinflussung der Calcium Ströme durch Chelatoren in elektrisch erregbaren und nicht erregbaren Zellen

Bödding, Matthias

1997

Author's details	vorgelegt von Matthias Bödding
Language	German
Size	94 S, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Tübingen, 1997
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Thesis: Beeinflussung der Calcium Ströme durch Chelatoren in elektrisch erregbaren und nicht erregbaren Zellen

Bödding, Matthias

1997

Author's details	vorgelegt von Matthias Bödding
Language	German
Size	94 S, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Tübingen, 1997
Database	Former special subject collection: coastal and deep sea fishing

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Article: Ca2+ dependence of the Ca2+-selective TRPV6 channel.

Bödding, Matthias / Flockerzi, Veit

The Journal of biological chemistry

2004 Volume 279, Issue 35, Page(s) 36546–36552

Abstract: Microfluorimetry and patch-clamp experiments were performed on TRPV6-expressing HEK cells to determine whether this Ca(2+)-sensing Ca(2+) channel is constitutively active. Intact cells loaded with fura-2 had an elevated intracellular free Ca(2+) ... ...

Abstract	Microfluorimetry and patch-clamp experiments were performed on TRPV6-expressing HEK cells to determine whether this Ca(2+)-sensing Ca(2+) channel is constitutively active. Intact cells loaded with fura-2 had an elevated intracellular free Ca(2+) concentration ([Ca(2+)](i)), which decreased to the same level such as in non-transfected cells if external Ca(2+) was chelated by EGTA. Whole cell recordings from non-transfected HEK cells and cells expressing human TRPV6 revealed the presence of a basal inward current in both types of cells when the internal solution contained 0.1 mm EGTA and 100 nm [Ca(2+)](i) or if the cytosolic Ca(2+) buffering remained undisturbed in perforated patch-clamp experiments. If recombinantly expressed TRPV6 forms open channels, one would expect Ca(2+)-induced current inhibition, because TRPV6 is negatively regulated by internal Ca(2+). However, dialyzing solutions with high [Ca(2+)] such as 1 microm into TRPV6-expressing cells did not block the basal inward current, which was not different from the recordings from non-transfected cells. In contrast, dialyzing 0.5 mm EGTA into TRPV6-expressing cells readily activated Ca(2+) inward currents, which were undetectable in non-transfected cells. Interestingly, monovalent cations permeated the TRPV6 channels under conditions where no Ca(2+) permeation was detectable, indicating that divalent cations block TRPV6 channels from the extracellular side. Like human TRPV6, the truncated human TRPV6(Delta695-725), which lacks the C-terminal domain required for Ca(2+)-calmodulin binding, does not form constitutive active channels, whereas the human TRPV6(D542A), carrying a point mutation in the presumed pore region, does not function as a channel. In summary, no constitutive open TRPV6 channels were detected in patch-clamp experiments from transfected HEK cells. However, channel activity is highly regulated by intracellular and extracellular divalent cations.
MeSH term(s)	Animals ; Biotinylation ; Blotting, Western ; Buffers ; Calcium/chemistry ; Calcium/metabolism ; Calcium Channels/chemistry ; Calcium Channels/metabolism ; Cations ; Cell Line ; Cell Line, Tumor ; Cell Membrane/metabolism ; Chelating Agents/pharmacology ; Cytosol/metabolism ; Egtazic Acid/pharmacology ; Electrophysiology ; Fluorescent Dyes/pharmacology ; Fura-2/pharmacology ; Humans ; Mutagenesis, Site-Directed ; Mutation ; Patch-Clamp Techniques ; Protein Binding ; Rats ; Recombinant Proteins/chemistry ; TRPV Cation Channels ; Time Factors ; Transfection
Chemical Substances	Buffers ; Calcium Channels ; Cations ; Chelating Agents ; Fluorescent Dyes ; Recombinant Proteins ; TRPV Cation Channels ; TRPV6 channel ; Egtazic Acid (526U7A2651) ; Calcium (SY7Q814VUP) ; Fura-2 (TSN3DL106G)
Language	English
Publishing date	2004-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M404679200
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