Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor.
The antigen receptors on B lymphocytes are cell-surface immunoglobulins. Antibodies against surface IgM (sIgM) coimmunoprecipitate several sIgM-associated proteins. Incubation of anti-IgM complexes with [gamma-32P]ATP leads to the phosphorylation on tyrosine of IgM-associated proteins including MB-1 and a protein of 72 kDa. Peptide mapping and reimmunoprecipitation experiments indicate that the 72-kDa phosphoprotein is PTK72, a protein-tyrosine kinase that is expressed at highest levels in B lymphocytes. MB-1 is also phosphorylated in immune complexes prepared with antibodies to PTK72, indicating that components of the IgM complex are associated with PTK72. In addition, PTK72 is associated with sIgD complexes isolated from spleen B lymphocytes. The cross-linking of sIgM antigen receptors on B lymphocytes leads to the rapid phosphorylation of PTK72 on tyrosine and to the activation of PTK72 as measured by autophosphorylation and by the phosphorylation of an exogenous substrate in anti-PTK72 immune complexes. These results suggest that the signaling cascade initiated by engagement of the B cell antigen receptor involves the increased enzymatic activity of PTK72, which is already present in a preformed antigen receptor complex.
Hutchcroft
J E
JE
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907.
Harrison
M L
ML
Geahlen
R L
RL
D002460:Cell Line; D003432:Cross-Linking Reagents; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008970:Molecular Weight; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases