Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation.
Lnk was originally cloned from a rat lymph node cDNA library and shown to participate in T cell signaling. Human Lnk (hLnk) was cloned by screening a Jurkat cell cDNA library. hLnk has a calculated molecular mass of 63 kDa, and its deduced amino acid sequence indicates the presence of ... an N-terminal proline-rich region, a pleckstrin homology domain, and a Src homology 2 domain. When expressed in COS cells, hLnk migrates with an apparent molecular mass of 75 kDa. Confocal fluorescence microscope analysis indicates that in COS cells transfected with an expression vector encoding a chimeric Lnk-green fluorescent protein, hLnk is found at the juxtanuclear compartment and also appears to be localized at the plasma membrane. Lnk is tyrosine-phosphorylated by p56lck. Following phosphorylation, p56lck binds to tyrosine-phosphorylated hLnk through its Src homology 2 domain. In COS cells cotransfected with hLnk, p56lck, and CD8-zeta, hLnk associated with tyrosine-phosphorylated TCR zeta-chain through its Src homology 2 domain. The overexpression of Lnk in Jurkat cells led to an inhibition of anti-CD3 mediated NF-AT-Luc activation. Our study reveals a potentially new mechanism of T cell-negative regulation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Blood Proteins, COS Cells, Carrier Proteins, DNA, Complementary, DNA-Binding Proteins, Enzyme Precursors, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Membrane Proteins, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Proteins, RNA, Messenger, Rats, Receptors, Antigen, T-Cell, Sequence Homology, Amino Acid, Signal Transduction, T-Lymphocytes, Transcription Factors, Transfection, Tyrosine, src Homology Domains
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Blood Proteins, COS Cells, Carrier Proteins, DNA, Complementary, DNA-Binding Proteins, Enzyme Precursors, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Membrane Proteins, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Proteins, RNA, Messenger, Rats, Receptors, Antigen, T-Cell, Sequence Homology, Amino Acid, Signal Transduction, T-Lymphocytes, Transcription Factors, Transfection, Tyrosine, src Homology Domains
J. Immunol.
Date: May. 15, 2000
PubMed ID: 10799879
View in: Pubmed Google Scholar
Download Curated Data For This Publication
4994
Switch View:
- Interactions 1