Cell cycle-specific activation of the PTK72 protein-tyrosine kinase in B lymphocytes.
The engagement of cell-surface antigen receptors on B lymphocytes by anti-IgM antibodies leads to the rapid tyrosine phosphorylation and activation of the protein-tyrosine kinase, PTK72. High concentrations of anti-IgM, which promote cell cycle entry and progression through G1, result in a biphasic change in the state of tyrosine phosphorylation of PTK72. An initial, rapid increase is seen within 5 min, which slowly declines to the level found in resting cells over a period of 9 h. A second increase is then observed 18-30 h following the initial stimulation. Low concentrations of anti-IgM, which promote cell cycle entry but not progression through G1, result only in the initial, rapid phosphorylation. The polyclonal mitogens lipopolysaccharide and dextran sulfate, which stimulate both cell cycle entry and progression to late G1, result only in the second, late phase of tyrosine phosphorylation. This second phase of elevated tyrosine phosphorylation is cell cycle-dependent, as demonstrated by its appearance in cells blocked at G1/S and absence in cells blocked at G2/M. The increase in the tyrosine phosphorylation of PTK72 is accompanied by an increase in its activity with no change in its concentration. These data suggest a possible second role for PTK72 in the commitment of activated B cells to proliferation.
Burg
D L
DL
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-1333.
Harrison
M L
ML
Geahlen
R L
RL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D002453:Cell Cycle; D002478:Cells, Cultured; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008934:Mitogens; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; C079492:PTK72; D011505:Protein-Tyrosine Kinases