Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig alpha and Ig beta association and signal transduction.
Potentiation of initial signal transduction events through the cross-linking of the B cell antigen receptor complex appears to be dependent upon the association of membrane immunoglobulin (mIg) with Ig alpha and Ig beta. We made two groups of mutations within the COOH terminus of mIgM substituting: 1) the spacer, transmembrane, and cytoplasmic domains and 2) the NH2-terminal 2-8 amino acids within the transmembrane domain (NLWTTAST). We then evaluated the ability of the mutated receptors to associate with Ig alpha and Ig beta and to initiate signal transduction events (Ca2+ mobilization and phosphorylation by tyrosine protein kinases) after cross-linking mIgM receptors. Mutant mIgM receptors containing substitutions of gamma 2b (spacer, transmembrane, and cytoplasmic domains), AA for TT, and AAAAA for TTAST bound Ig alpha and Ig beta and initiated signal transduction events after mIgM receptor cross-linking. However, substitutions of I-A alpha (spacer, transmembrane, and cytoplasmic domains) or TTVVCALGL for NLWTTAST blocked association of Ig alpha and Ig beta and initiation of signal transduction events. Results indicate that residues within the first 8 amino acids of the transmembrane domain other than TTAST are necessary for receptor function and association with Ig alpha and Ig beta.
Michnoff
C H
CH
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Parikh
V S
VS
Lelsz
D L
DL
Tucker
P W
PW
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051925:CD79 Antigens; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D051925:CD79 Antigens; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D014443:Tyrosine; D002118:Calcium