Role of two conserved cytoplasmic threonine residues (T410 and T412) in CD5 signaling.
CD5 is a transmembrane coreceptor that modulates activation and differentiation signals mediated by the Ag-specific receptor present on both T and B1a lymphocytes. CD5 lacks intrinsic catalytic activity, and its immunomodulatory properties result from intracellular interactions mediated by the CD5 cytoplasmic tail. The nature of these interactions is currently a matter of investigation. Here, we present a selective mutagenesis analysis of two conserved threonine residues (T410 and T412) located at the membrane-proximal cytoplasmic region of CD5. These residues are contained within consensus phosphorylation motifs for protein kinase C and are shown here to be critical for in vivo protein kinase C-mediated phosphorylation of CD5. Functional studies revealed that the integrity of T410 and T412 is also critical for CD5-mediated phosphatidylcholine-specific phospholipase C (PC-PLC) activation and phorbol ester-mediated inhibition of Ab-induced internalization of CD5. These results strongly argue in favor of a role for T410 and T412 in the signaling mediated by CD5.
Vilà
J M
JM
Servei d'Immunologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
Calvo
J
J
Places
L
L
Padilla
O
O
Arman
M
M
Gimferrer
I
I
Aussel
C
C
Vives
J
J
Lozano
F
F
D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D017124:Conserved Sequence; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013912:Threonine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D004075:Diglycerides; D010446:Peptide Fragments; D013912:Threonine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate