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 R NA splicing. Both CD2BP1 molecules are homologous to Schizosaccharomyces po mbe cdc15, and include a helical domain, variable length intervening PEST s equence and C-terminal SH3 domain. Although the CD2BP1 SH3 domain binds dir ectly to the CD2 sequence, KGPPLPRPRV (amino acids 300-309), its associatio n is augmented markedly by the CD2BP1 N-terminal segment. Upon ligand-induc ed clustering of surface CD2 molecules, CD2BP1 redistributes from a cytosol ic to a surface membrane compartment, co-localizing with CD2, In turn, CD2- stimulated adhesion is down-regulated by CD2BP1, apparently through couplin g of the protein tyrosine phosphatase (PTP)-PEST to CD2, These findings off er the first molecular view into the control processes for T cell adhesion.