title: Continual signaling is responsible for constitutive ERK phosphorylation in B-1a cells.
abstract: B-1a cells constitutively express phosphorylated, activated ERK, but the origin of pERK in B-1 cells has not been determined. To address this issue, we examined specific mediators of intracellular signaling in unmanipulated B-1a cells. We found that constitutive pERK was rapidly lost from B-1a cells following addition of metabolic inhibitors that block src kinase, Syk, PI-3K, and PLC function. We examined Syk and PLC in more detail and found rapid accumulation of phosphorylated forms of these molecules in B-1a cells, but not B-2 cells, when phosphatase activity was inhibited, and this change occurred in the majority of B-1a cells. Further, we showed that inhibition of src kinase activity eliminated "downstream" pSyk and pPLC accumulation in phosphatase-inhibited B-1a cells, indicating a pathway connection. CD86 expression is greater on B-1 than B-2 cells and plays a role in antigen presentation by B-1 cells to T cells. We found that when Syk or PI-3K was inhibited, CD86 expression was diminished in a reversible fashion. All together, these results indicate that continual activation of intracellular signaling leads to constitutive activation of ERK in B-1 cells, with attendant consequences for co-stimulatory molecule expression.
authors: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors: Nichol E
authors: NE
authors: Holodick
authors: Joseph R
authors: JR
authors: Tumang
authors: Thomas L
authors: TL
authors: Rothstein
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051940:B7-2 Antigen / Q000187:drug effects / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000072377:Syk Kinase; D014638:Vanadates / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D018956:CD5 Antigens; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010744:Phosphoric Monoester Hydrolases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D014638:Vanadates; D019061:src-Family Kinases; C526836:Cd5 protein, mouse; C497965:Cd86 protein, mouse; C076715:pervanadate; C000606897:Syk protein, mouse