S100B-RAGE-mediated augmentation of angiotensin II-induced activation of JAK2 in vascular smooth muscle cells is dependent on PLD2.
Angiotensin II (Ang II), a vasoactive peptide that is also considered a growth factor, has been implicated in both normal and diabetic cellular proliferation. We recently found that activation of janus kinase 2 (JAK2) is essential for the Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) and that high glucose augments Ang II-induced proliferation of VSMCs by increasing signal transduction through activation of JAK2. Here, we demonstrate that S100B, a ligand for the receptor of advanced glycation end products (RAGEs), augmented both Ang II-induced tyrosine phosphorylation of JAK2 and cell proliferation in VSMCs in a receptor-dependent manner. We also found that S100B-RAGE interaction triggered intracellular generation of reactive oxygen species (ROS), VSMC proliferation, and JAK2 tyrosine phosphorylation via activation of phospholipase D (PLD)2. These results provide direct evidence for linkages between PLD2, ROS production, and S100B-RAGE-induced enhancement of Ang II-induced cell proliferation and activation of JAK2 in VSMCs.
Shaw
Sean S
SS
Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA.
Schmidt
Ann Marie
AM
Banes
Amy K
AK
Wang
Xiaodan
X
Stern
David M
DM
Marrero
Mario B
MB
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D018274:Electroporation; D006861:Hydrogen Peroxide / Q000378:metabolism; D053614:Janus Kinase 2; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism / Q000494:pharmacology*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000906:Antibodies; D004268:DNA-Binding Proteins; D008024:Ligands; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; C110294:S100A1 protein; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D014443:Tyrosine; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; C105606:phospholipase D2; D010739:Phospholipase D