TAILIEUCHUNG - báo cáo khoa hoc : Novel roles for biogenic monoamines: from monoamines in transglutaminase-mediated post-translational protein modification to monoaminylation deregulation diseases

Functional protein serotonylation is a newly recognized post-translational modification with the primary biogenic monoamine (PBMA) serotonin (5-HT). This covalent protein modification is catalyzed by transglutaminas-es (TGs) and, for example, acts in the constitutive activation of small GTP-ases. | IFEBS Journal MINIREVIEW Novel roles for biogenic monoamines from monoamines in transglutaminase-mediated post-translational protein modification to monoaminylation deregulation diseases Diego J. Walther Silke Stahlberg and Jakob Vowinckel Neurochemistry Group and Mouse Lab Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Berlin Germany Keywords dopaminylation histaminylation norepinephrinylation primary biogenic monoamine serotonylation smallGTPases TG2 TPH transglutaminase tryptophan hydroxylase Correspondence D. J. Walther Max Planck Institute for Molecular Genetics Ihnestrasse 73 14195 Berlin Germany Fax 49 30 8413 1383 Tel 49 30 8413 1664 E-mail dwalther@ Received 6 April 2011 revised 3 August 2011 accepted 24 August 2011 doi Functional protein serotonylation is a newly recognized post-translational modification with the primary biogenic monoamine PBMA serotonin 5-HT . This covalent protein modification is catalyzed by transglutaminases TGs and for example acts in the constitutive activation of small GTP-ases. Multiple physiological roles have been identified since its description in 2003 and importantly deregulated serotonylation was shown in the etiology of bleeding disorders primary pulmonary hypertension and diabetes. The PBMAs 5-HT histamine dopamine and norepinephrine all act as neurotransmitters in the nervous system and as hormones in non-neuronal tissues which points out their physiological importance. In analogy to se-rotonylation we have found that also the other PBMAs act through the TG-catalyzed mechanisms of histaminylation dopaminylation and nor-epinephrinylation . Therefore PBMAs deploy a considerable portion of their effects via protein monoaminylation in addition to their canonical receptor-mediated signaling. Here the implications of these newly identified post-translational modifications are presented and discussed. Furthermore the potential regulatory roles of

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