A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion.
A human CD2 cytoplasmic tail-binding protein, termed CD2BP1, was identified by an interaction trap cloning method. Expression of CD2BP1 is restricted to hematopoietic tissue, being prominent in T and natural killer (NK) cells, with long (CD2BP1L) and short (CD2BP1S) variants arising by alternative RNA splicing. Both CD2BP1 molecules are homologous to Schizosaccharomyces pombe cdc15, and include a helical domain, variable length intervening PEST sequence and C-terminal SH3 domain. Although the CD2BP1 SH3 domain binds directly to the CD2 sequence, KGPPLPRPRV (amino acids 300-309), its association is augmented markedly by the CD2BP1 N-terminal segment. Upon ligand-induced clustering of surface CD2 molecules, CD2BP1 redistributes from a cytosolic to a surface membrane compartment, co-localizing with CD2. In turn, CD2-stimulated adhesion is downregulated by CD2BP1, apparently through coupling of the protein tyrosine phosphatase (PTP)-PEST to CD2. These findings offer the first molecular view into the control processes for T cell adhesion.
Li
J
J
Laboratory of Immunobiology, Harvard Medical School, 44 Binney Street J318, Boston, MA 02115, USA.
Nishizawa
K
K
An
W
W
Hussey
R E
RE
Lialios
F E
FE
Salgia
R
R
Sunder-Plassmann
R
R
Reinherz
E L
EL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001665:Binding Sites; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D018968:CD58 Antigens / Q000276:immunology; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D003001:Cloning, Molecular; D003593:Cytoplasm; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007152:Immunologic Capping; D007962:Leukocytes; D008969:Molecular Sequence Data; D011485:Protein Binding; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013154:Spleen; D013950:Thymus Gland; D014018:Tissue Distribution; D018909:src Homology Domains
D018801:CD2 Antigens; D018968:CD58 Antigens; C082279:CDC15 protein; D018797:Cell Cycle Proteins; C516738:PTPN12 protein, human; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins