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PMID: 7688784 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.

The Journal of experimental medicine ·Vol. 178 ·No. 3 ·1993-09-01 ·Pages 1049-55

Sanchez M, Misulovin Z, Burkhardt AL, Mahajan S, Costa T, Franke R, Bolen JB, Nussenzweig M

Abstract

Immunoglobulin (Ig) antigen receptors are composed of a noncovalently-associated complex of Ig and two other proteins, Ig alpha and Ig beta. The cytoplasmic domain of both of these Ig associated proteins contains a consensus sequence that is shared with the signaling proteins of the T cell and Fc receptor. To test the idea that Ig alpha-Ig beta heterodimers are the signaling components of the Ig receptor, we have studied Ig mutations that interfere with signal transduction. We find that specific mutations in the transmembrane domain of Ig that inactivate Ca2+ and phosphorylation responses also uncouple IgM from Ig alpha-Ig beta. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Ig alpha with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig beta to the inactive Ig reconstitutes only Ca2+ responses. Thus, Ig alpha and Ig beta are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that Ig alpha and Ig beta can activate different signaling pathways.

MeSH Terms
Amino Acid Sequence Antigens, CD CD79 Antigens Calcium/metabolism Cytoplasm/ultrastructure DNA Mutational Analysis Enzyme Activation Humans Immunoglobulin M/metabolism Immunoglobulin alpha-Chains/physiology In Vitro Techniques Macromolecular Substances Membrane Glycoproteins/chemistry,physiology Molecular Sequence Data Phosphoproteins/metabolism Phosphorylation Phosphotyrosine Protein-Tyrosine Kinases/metabolism Receptor Aggregation Receptors, Antigen, B-Cell/chemistry,physiology Signal Transduction Tyrosine/analogs & derivatives,metabolism
Chemicals
Antigens, CD CD79 Antigens CD79A protein, human Immunoglobulin M Immunoglobulin alpha-Chains Macromolecular Substances Membrane Glycoproteins Phosphoproteins Receptors, Antigen, B-Cell Phosphotyrosine Tyrosine Protein-Tyrosine Kinases Calcium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sanchez M
Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021.
Misulovin Z
Burkhardt A L
Mahajan S
Costa T
Franke R
Bolen J B
Nussenzweig M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.178.3.1049
Published
1993-09-01
Pages
1049-55
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191166
Subset
IM
Grants
NIAID NIH HHS · AI-33890-01 · United States
External Links
PubMed source DOI: 10.1084/jem.178.3.1049 PMC Full Text View journal details
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