Biomaterial Database

Biosynthesis and post-translational modification of CD6, a T cell signal-transducing molecule. 1991

J A Swack, and J W Mier, and P L Romain, and S R Hull, and C E Rudd

Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts.

CD6 (T12) is a 130-kDa glycoprotein present on the surface of human T cells. Previously, we demonstrated that the anti-T12 and anti-2H1 monoclonal antibodies recognized different epitopes on CD6, and both were capable of transducing activation signals to T cells. Anti-T12 augmented suboptimal signaling via the TCR/CD3 complex and directly activated separated CD4+ but not CD8+ cells. Structural characterization of CD6 revealed that it contained intrachain disulfide bonds, was N-glycosylated, and in activated cells was phosphorylated on serine. Given the functional significance of CD6 and its involvement in signaling via CD3 and CD2 pathways, we examined in detail the biosynthesis, structural characteristics, and phosphorylation properties of this receptor-like molecule. These studies demonstrate that the nascent CD6 polypeptide on both T cells and thymocytes in 88 kDa, and the immature N-glycosylated form is 110 kDa. After maturation of N-linked glycan and addition of sulfated O-linked oligosaccharide, CD6 appears on the cell surface as a molecule of 130 kDa. CD6 is phosphorylated in resting cells and can be hyperphosphorylated when stimulated by phorbol 12-myristate 13-acetate, indicating that it may participate in the major common signaling pathway mediated through protein kinase C. Concanavalin A-activated cells are phosphorylated at an additional site(s) on the molecule and cannot be hyperphosphorylated with phorbol 12-myristate 13-acetate. These physical features reveal additional clues about the physiological role of CD6 and its mechanism of signal transduction and strongly suggest that CD6 represents a physiologically important membrane receptor involved in T cell activation.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D011499	Protein Processing, Post-Translational	Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.	Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000945	Antigens, Differentiation, T-Lymphocyte	Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.	Antigens, Differentiation, T-Cell,Differentiation Antigens, T-Cell,L3T4 Antigens,Leu Antigens, T-Lymphocyte,T-Cell Differentiation Antigens,T-Lymphocyte Differentiation Antigens,T6 Antigens,Antigens, Differentiation, T Lymphocyte,Differentiation Antigens, T Lymphocyte,Antigens, L3T4,Antigens, T-Cell Differentiation,Antigens, T-Lymphocyte Differentiation,Antigens, T-Lymphocyte Leu,Antigens, T6,Differentiation Antigens, T Cell,Differentiation Antigens, T-Lymphocyte,Leu Antigens, T Lymphocyte,T Cell Differentiation Antigens,T Lymphocyte Differentiation Antigens,T-Lymphocyte Leu Antigens
D013601	T-Lymphocytes	Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.	T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014415	Tunicamycin	An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms.
D015375	Receptors, Interleukin-2	Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.	IL-2 Receptors,Interleukin-2 Receptor,Interleukin-2 Receptors,Receptors, IL-2,Receptors, T-Cell Growth Factor,T-Cell Growth Factor Receptors,IL-2 Receptor,IL2 Receptor,IL2 Receptors,Interleukin 2 Receptor,Receptor, TCGF,T-Cell Growth Factor Receptor,TCGF Receptor,TCGF Receptors,IL 2 Receptor,IL 2 Receptors,Interleukin 2 Receptors,Receptor, IL-2,Receptor, IL2,Receptor, Interleukin 2,Receptor, Interleukin-2,Receptors, IL 2,Receptors, IL2,Receptors, Interleukin 2,Receptors, T Cell Growth Factor,Receptors, TCGF,T Cell Growth Factor Receptor,T Cell Growth Factor Receptors