The CD19 complex of B lymphocytes. Activation of phospholipase C by a protein tyrosine kinase-dependent pathway that can be enhanced by the membrane IgM complex.
We have investigated the mechanism by which the membrane protein complex of the B lymphocyte that contains CD19 and CR2 activates phospholipase C (PLC) to induce a rise in [CA2+]i. The CD19 complex resembled the membrane IgM complex in that three protein tyrosine kinase inhibitors suppressed increases in [Ca2+]i and inositol bisphosphate and inositol triphosphate generation. However, the activation of PLC by the CD19 complex could be distinguished from that by the membrane IgM complex by slower kinetics of generation of inositol phosphates, resistance to inhibition by activators of protein kinase C, and different pattern of tyrosine-phosphorylated cellular substrates. Western blot analysis of lysates from cells stimulated by the CD19 complex demonstrated a single new phosphotyrosine-containing protein of 85 kDa, whereas multiple other phosphotyrosine-containing proteins were present in cells activated by the mIgM complex. In particular, PLC-gamma 1, which is a substrate for the protein tyrosine kinase activated by the mIgM complex, was not tyrosine-phosphorylated in cells stimulated by the CD19 complex. Cross-linking the two complexes together caused a synergistic increase in [CA2+]i which was neither suppressed by activation of protein kinase C nor associated with increased tyrosine-phosphorylation of PLC, characteristic of the CD19 pathway. Therefore, the B cell has two signal transduction complexes, associated with membrane IgM and CD19, that activate PLC by different mechanisms and that can synergistically interact to enhance this function by the CD19 pathway.
Carter
R H
RH
Division of Molecular and Clinical Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Tuveson
D A
DA
Park
D J
DJ
Rhee
S G
SG
Fearon
D T
DT
D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008970:Molecular Weight; D010703:Phorbol Esters / Q000494:pharmacology; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011951:Receptors, Complement / Q000502:physiology*; D017464:Receptors, Complement 3d; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D007295:Inositol Phosphates; D046911:Macromolecular Substances; D010703:Phorbol Esters; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D002118:Calcium