Regulation and Function of Skap-55 Non-canonical Motif Binding to the Sh3c Domain of Adhesion and Degranulation-promoting Adaptor Protein.
From: Department of Medical Oncology and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. jonathan_duke-cohan@dfci.harvard.edu
The Journal of biological chemistry
- Publish Date: May 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 19
- Pages: 13743-50
- Medium: Print
- Language: English
- Citation (JAMA): Duke-Cohan Jonathan S, Kang Hyun, Liu Hebin, et al. Regulation and Function of Skap-55 Non-canonical Motif Binding to the Sh3c Domain of Adhesion and Degranulation-promoting Adaptor Protein.. J. Biol. Chem. May 2006;281:13743-50
Abstract
The immune cell adaptor adhesion and degranulation promoting adaptor protein (ADAP) and its binding to T-cell adaptor Src kinase-associated protein of 55 kDa (SKAP-55) play a key role in the modulation of T-cell adhesion. While primary binding occurs via SKAP-55 SH3 domain binding to a proline-rich region in ADAP, a second interaction occurs between the ADAP C-terminal SH3 domain (ADAP-SH3c) and a non-canonical RKXXY294XXY297 motif in SKAP-55. Increasing numbers of non-canonical SH3 domain binding motifs have been identified in a number of biological systems. The presence of tyrosine residues in the SKAP-55 RKXXY294XXY297 motif suggested that phosphorylation might influence this unusual SH3 domain interaction. Here, we show that the Src kinase p59fyn can induce the in vivo phosphorylation of the motif, and this event blocks ADAP-SH3c domain binding to the peptide motif. The importance of tyrosine phosphorylation was confirmed by plasmon resonance interaction analysis showing that phosphorylation of Tyr294 residue plays a central role in mediating dissociation, whereas phosphorylation of the second Tyr297 had no effect. Although loss of this secondary interaction did not result in the disruption of the complex, the Y294F mutation blocked T-cell receptor-induced up-regulation of lymphocyte function-associated antigen-1-mediated adhesion to intercellular adhesion molecule-1 and interleukin-2 promoter activity. Our findings identify a RKXXY294 motif in SKAP-55 that mediates unique ADAP SH3c domain binding and is needed for LFA-1-mediated adhesion and cytokine production.
Mesh Headings (Keywords): Amino Acid Motifs, Amino Acid Substitution, Animals, Binding Sites, COS Cells, Cell Adhesion, Cercopithecus aethiops, Cytokines, Humans, Jurkat Cells, Lymphocyte Function-Associated Antigen-1, Lymphocytes, Phosphoproteins, Phosphorylation, Protein Binding, src Homology Domains
Check for Full Text / PubMed Unique Identifier (PMID): 16461356
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.