Mechanisms of protein A superantigen-induced signal transduction for proliferation of mouse B cell.
Apart from many of the biological properties of protein A (PA) of Staphylococcus aureus, it has been recognized recently as a B-cell superantigen. Therefore, we investigated the molecular mechanisms of PA superantigen-induced mice splenic B-cell proliferation. Treatment of resting B cells with PA-evoked cell proliferation. Binding of PA to B cells led to a cascade of signal transduction mechanisms involving tyrosine kinase that activated phospholipase C, which in turn activated protein kinase C (PKC), and translocated it from cytosol to membrane. Mitogen-activated protein (MAP) kinase has been found to be activated down-stream of PKC in this signal pathway, which ultimately caused an activation of serum-responsive factor (SRF). Inhibition at any step of this signaling cascade could block B-cell proliferation. PA could also stimulate the Bcl-2 gene expression at protein level thereby supporting the pro-proliferative effect of PA. Thus, the molecular mechanisms related to PA-induced B cell proliferation has been delineated in this report as tyrosine kinase > PLC > PKC > MAP kinase > SRF > Bcl-2. Knowledge gathered from these observations might be of immense help to study the immune cell proliferation as a part of immunoactivation process. Also, the development of suitable inhibitors of the signaling pathway outlined here might provide clues as to how to abrogate pathologic antibody production in many disease processes.
Das
T
T
Immunotechnology Section, Bose Institute, Calcutta, India.
Sa
G
G
Ray
P K
PK
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D026362:Serum Response Factor; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013205:Staphylococcal Protein A / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D010738:Type C Phospholipases / Q000502:physiology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D026362:Serum Response Factor; D013205:Staphylococcal Protein A; D018089:Superantigens; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases