The B cell antigen receptor complex: mechanisms and implications of tyrosine kinase activation.
The B cell receptor is a multimeric receptor complex whose constituent chains appear to mediate distinct and possibly interrelated functions. In this review we have focused on how one chain, immunoglobulin (Ig)-alpha, may function to activate tyrosine kinases and the consequences of that activation. The cytoplasmic domain of Ig-alpha contains a consensus sequence, the antigen recognition homology 1 (ARH 1) motif, which is found in Ig-beta and other antigen recognition receptor associated chains. We argue that this conserved structure reflects an underlying conserved mechanism of secondary effector activation. Our data also indicates that the specificity of each motif (i.e., the elements which restrict secondary effector binding to particular motifs) is encoded within divergent sequences found in each ARH 1 motif. In the particular case of kinase activation by Ig-alpha, the subsequent phosphorylation of multiple tyrosines on Ig-alpha, Ig-beta, CD19, CD22 and possibly other functionally related chains form recruitment sites for a myriad of secondary signal transducers. In this model, proximal tyrosine kinases and phosphatases do not function so much to mediate the linear transfer of information as to establish and modulate an interrelated network of signal transducers capable of driving complicated cellular responses.
Tseng
J
J
Department of Medicine, University of Chicago, IL 60637, USA.
Lee
Y J
YJ
Eisfelder
B J
BJ
Clark
M R
MR
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D051925:CD79 Antigens; D015815:Cell Adhesion Molecules; D016384:Consensus Sequence / Q000276:immunology / Q000502:physiology; D004789:Enzyme Activation / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology; D037102:Lectins; D017493:Leukocyte Common Antigens / Q000378:metabolism; D018448:Models, Immunological; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D051925:CD79 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens