title: CB1 cannabinoid receptor-mediated tyrosine phosphorylation of focal adhesion kinase-related non-kinase.
abstract: The effect of cannabinoid on the tyrosine phosphorylation of focal adhesion kinase (FAK) and focal adhesion kinase-related non-kinase (FRNK) was investigated in differentiated mouse neuroblastoma N1E-115 cells. HU-210, a potent cannabinoid agonist, elicited a time-dependent enhancement of tyrosine phosphorylation of FRNK, but not FAK. Pretreatment of cells with antisense oligodeoxynucleotide targeting CB1 cannabinoid receptor abolished HU-210-induced FRNK tyrosine phosphorylation. In addition, pretreatment of cells with 8-Br-cAMP also blocked HU-210-induced FRNK tyrosine phosphorylation. These data demonstrated that HU-210 induces FRNK tyrosine phosphorylation by activating G(i)-coupled CB1 cannabinoid receptor in N1E-115 cells. This newly discovered, cannabinoid-induced FRNK tyrosine phosphorylation might be a novel mechanism for cannabinoid-induced functional changes.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Z H
authors.initials: ZH
authors.lastname: Song
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D020536:Enzyme Activators; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014443:Tyrosine; D013759:Dronabinol; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; C062018:HU 211