Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor.
Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T-cell receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have studied signal transduction by chimeric immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin-2 secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.
Burkhardt
A L
AL
Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021.
Costa
T
T
Misulovin
Z
Z
Stealy
B
B
Bolen
J B
JB
Nussenzweig
M C
MC
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000378:metabolism*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007376:Interleukin-2; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D002118:Calcium