Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and phosphorylated Ig-alpha.
Among the earliest detectable events in B-cell antigen receptor-mediated signal transduction are the activation of receptor-associated Src-family tyrosine kinases and the tyrosine phosphorylation of Ig-alpha and Ig-beta receptor subunits. These kinases appear to interact with resting B-cell antigen receptor complexes primarily through the Ig-alpha chain antigen receptor homology 1 (ARH1) motif. Recent studies showed a dramatic increase in the amount of Src-family kinase p59fyn bound to Ig-alpha when ARH1 motif tyrosines were phosphorylated. To explore the submolecular basis of these interactions, we conducted mutational analysis to localize sites in p53/56lyn and p59fyn that bind nonphosphorylated and phosphorylated Ig-alpha. Here we report that distinct regions within these kinases bind nonphosphorylated and phosphorylated Ig-alpha ARH1 motifs. The N-terminal 10 residues mediate binding to the nonphosphorylated Ig-alpha ARH1 motif. Association with the phosphorylated Ig-alpha ARH1 motif is mediated by Src homology 2 domains. These findings suggest a mechanism whereby ligand-induced Ig-alpha tyrosine phosphorylation initiates a change in the orientation of an associated kinase that may alter its activity and/or access to substrates and other effectors.
Pleiman
C M
CM
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Abrams
C
C
Gauen
L T
LT
Bedzyk
W
W
Jongstra
J
J
Shaw
A S
AS
Cambier
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D001483:Base Sequence; D051925:CD79 Antigens; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D019061:src-Family Kinases
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; D017931:DNA Primers; D008562:Membrane Glycoproteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases