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Molecular and Cellular Biochemistry

, Volume 372, Issue 1–2, pp 211–220 | Cite as

Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC–PKC–CaMK II- and Janus kinase-dependent signaling pathway

  • Wagner Santos Coelho
  • Mauro Sola-Penna
Article

Abstract

Serotonin (5-HT) is a hormone that has been implicated in the regulation of many physiological and pathological events. One of the most intriguing properties of this hormone is its ability to up-regulate mitosis. Moreover, 5-HT stimulates glucose uptake and up-regulates PFK activity through the 5-HT2A receptor, resulting in the phosphorylation of a tyrosine residue of PFK and the intracellular redistribution of PFK within skeletal muscle. The present study investigated some of the signaling intermediates involved in the effects of 5-HT on 6-phosphofructo-1-kinase (PFK) regulation from skeletal muscle using kinetic assessments, immunoprecipitation, and western blotting assays. Our results demonstrate that 5-HT stimulates PFK from skeletal muscle via phospholipase C (PLC). The activation of PLC in skeletal muscle leads to the recruitment of protein kinase C (PKC) and calmodulin and the stimulation of calmodulin kinase II, which associates with PFK upon 5-HT action. Alternatively, 5-HT loses its ability to up-regulate PFK activity when Janus kinase is inhibited, suggesting that 5-HT is able to control glycolytic flux in the skeletal muscle of mice by recruiting different pathways and controlling PFK activity.

Keywords

Glycolysis Phosphofructokinase Regulation Metabolism Hormone 

Abbreviations

5-HT

5-Hydroxytryptamine, serotonin

CaMK II

Calcium–calmodulin-dependent protein kinase type II

f-actin

Filamentous actin

F6P

Fructose-6-phosphate

GLUT

Glucose transporter

GPCRs

G-protein-coupled receptors

KN-62

1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine

PFK

6-Phosphofructo-1-kinase

PI3 K

Phosphatidylinositol-3-phosphate kinase

PKC

Protein kinase C

PLC

Phospholipase C

PMA

Phorbol-12-myristate-13-acetate

Notes

Acknowledgments

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Programa de Oncobiologia) and Programa de Núcleos de Excelência (PRONEX).

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de FármacosFaculdade de Farmácia, Universidade Federal do Rio de JaneiroIlha do Fundão, Rio de JaneiroBrazil
  2. 2.Instituto de Bioquímica MédicaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

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