Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins.
Melatonin is a pineal hormone involved in neuroendocrine processes in mammals. It has been shown that melatonin inhibits the enzymatic activities of adenylyl cyclases and the transcriptional activities of CREB. In this report, we demonstrate that 2-iodomelatonin (2IMT) treatment on COS-7 cells transfected with melatonin receptors (mt1 and MT2) induces c-Jun N-terminal kinase (JNK) activation, which is pertussis toxin (PTX)-sensitive, Ras/Rac-dependent and may involve Src-family protein tyrosine kinases. Moreover, PTX-insensitive Gs, Gz and G16 are capable of linking activated melatonin receptors to the stimulation of JNK. Agonist stimulation on PTX-pretreated COS-7 cells overexpressing mt1 receptor, Galpha(s) and adenylyl cyclase VI led to increased cAMP accumulation. Stimulation of endogenous mt1 receptors in MCF-7 cells was associated with the activation of both JNK and extracellular signal-regulated kinase (ERK). This report demonstrates the stimulatory effect of melatonin receptors on JNK, and provides experimental evidence for a functional coupling between the G(i)-coupled melatonin receptor and Gs, in terms of adenylyl cyclase activation.
Chan
Anthony S L
AS
Department of Biochemistry the Biotechnology Research Institute, and the Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Lai
Frank P L
FP
Lo
Rico K H
RK
Voyno-Yasenetskaya
Tatyana A
TA
Stanbridge
Eric J
EJ
Wong
Yung H
YH
D037361:Adenylate Cyclase Toxin; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D044385:GTP-Binding Protein alpha Subunits; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008970:Molecular Weight; D037342:Pertussis Toxin; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D044094:Receptors, Melatonin; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; C099387:GNAZ protein, human; D044385:GTP-Binding Protein alpha Subunits; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; C044556:2-iodomelatonin; D037342:Pertussis Toxin; D048056:Mitogen-Activated Protein Kinase 9; D019061:src-Family Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C112631:G protein alpha 16; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D020830:rac1 GTP-Binding Protein; D008550:Melatonin