Human CD5 signaling and constitutive phosphorylation of C-terminal serine residues by casein kinase II.
CD5 is a lymphocyte surface glycoprotein with a long cytoplasmic domain suitable for phosphorylation and signal transduction, which is involved in the modulation of Ag-specific receptor-mediated activation and differentiation signals. In this study, we use Jurkat T cell transfectants of CD5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase II (CKII) is responsible for the constitutive phosphorylation of CD5 molecules at a cluster of three serine residues located at the extreme C terminus (S458, S459, and S461). Furthermore, the yeast two-hybrid system demonstrates the specific association between the C-terminal regions of the CD5 cytoplasmic tail and the regulatory beta subunit of CKII. We demonstrate that CKII associates with and phosphorylates the C-terminal region of CD5, a conserved domain known to be relevant for the generation of second lipid messengers, and thereby enables at least one component of its signaling function.
Calvo
J
J
Servei d'Immunologia, Institut d'Investigacions Biomédiques August Pii Sunger, Hospital Clínic, Barcelona, Spain.
Vildà
J M
JM
Places
L
L
Simarro
M
M
Padilla
O
O
Andreu
D
D
Campbell
K S
KS
Aussel
C
C
Lozano
F
F
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000276:immunology; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047390:Casein Kinase II; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013379:Substrate Specificity / Q000276:immunology
D018956:CD5 Antigens; D004075:Diglycerides; D010446:Peptide Fragments; D012694:Serine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases