Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins occurs in response to antigen-receptor ligation in B cells and constitutively in pre-B cells.
Proteins that bind to discrete domains of the Blk, Fyn, Lyn, and Btk protein tyrosine kinases were examined in pre-B cells that had not been subjected to any external stimulation, as well as in nonstimulated and antigen-receptor-ligated B cells. Proteins that bind to the Src homology 2 domains of Blk and Fyn were identified in B cells that had been activated with anti-IgM but were not identified in unstimulated B cells. A number of Blk and Fyn Src homology 2 domain-binding phosphoproteins were also observed in pre-B cells that had not been stimulated in vitro. The phosphoproteins seen in activated B cells potentially represent substrates that play a role in the pathway of antigen-receptor-mediated signaling. Distinct signaling pathways involving distinguishable kinase substrates may be relevant in pre-B-cell-receptor-mediated cell survival during ontogeny. These results indirectly support models that predict constitutive ligand-independent signaling by the pre-antigen receptor during lymphoid ontogeny.
Aoki
Y
Y
Cancer Center, Massachusetts General Hospital, Boston 02129.
Isselbacher
K J
KJ
Cherayil
B J
BJ
Pillai
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D017931:DNA Primers; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D019061:src-Family Kinases
D017931:DNA Primers; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D005982:Glutathione Transferase; C082599:protein-tyrosine kinase p55(blk); D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases