Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85.
Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.
Hutchings
Nicholas J
NJ
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
Clarkson
Nicholas
N
Chalkley
Robert
R
Barclay
A Neil
AN
Brown
Marion H
MH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D018801:CD2 Antigens / Q000737:chemistry* / Q000378:metabolism; D051347:CapZ Actin Capping Protein; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D015398:Signal Transduction / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000276:immunology*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C495842:CAPZA1 protein, human; D018801:CD2 Antigens; C114545:CD2-associated protein; D051347:CapZ Actin Capping Protein; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; C433810:SH3KBP1 protein, human