Tyrosine Phosphorylation of Adaptor Protein 3BP2 Induces T Cell Receptor-Mediated Activation of Transcription Factor

Molecular adaptors/scaffolds have indispensable roles in the activation of lymphocytes. In this report, we have demonstrated the role of tyrosine phosphorylation of an adaptor protein 3BP2 (c-Abl-SH3 domain binding protein-2, also known as SH3BP2) in T cell receptor (TCR)-mediated activation of tran...

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Bibliographic Details
Published in:Biochemistry (Easton) 2005-03, Vol.44 (10), p.3891-3898
Main Authors: Qu, Xiujuan, Kawauchi-Kamata, Keiko, Miah, S. M. Shahjahan, Hatani, Tomoko, Yamamura, Hirohei, Sada, Kiyonao
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - antagonists & inhibitors
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Adaptor Proteins, Signal Transducing - physiology
Amino Acid Substitution - genetics
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Homeodomain Proteins - antagonists & inhibitors
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Homeodomain Proteins - physiology
Humans
Interleukin-2 - antagonists & inhibitors
Interleukin-2 - genetics
Interleukin-2 - metabolism
Jurkat Cells
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism
Membrane Microdomains - genetics
Membrane Microdomains - metabolism
NFATC Transcription Factors
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Phosphorylation
Promoter Regions, Genetic
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-vav
Receptors, Antigen, T-Cell - antagonists & inhibitors
Receptors, Antigen, T-Cell - physiology
RNA, Small Interfering - chemistry
src Homology Domains - genetics
Transcription Factors - antagonists & inhibitors
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation - genetics
Transfection
Tyrosine - genetics
Tyrosine - metabolism
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Summary:Molecular adaptors/scaffolds have indispensable roles in the activation of lymphocytes. In this report, we have demonstrated the role of tyrosine phosphorylation of an adaptor protein 3BP2 (c-Abl-SH3 domain binding protein-2, also known as SH3BP2) in T cell receptor (TCR)-mediated activation of transcription factor. Short interfering RNA for 3BP2 suppresses the expression level of endogenous 3BP2 and inhibits TCR-mediated activation of interleukin (IL)-2 promoter and nuclear factor of activated T cells (NFAT) element. Engagement of TCR induces tyrosine phosphorylation and lipid raft translocation of 3BP2. The overexpression studies reveal that substitution of 3BP2-Tyr183, Tyr446, or Arg486 in the SH2 domain suppresses TCR-mediated activation of NFAT. Point mutations of 3BP2 cannot affect the translocation of 3BP2 into the lipid raft. Phosphorylation of Tyr183 is required for the interaction with Vav1, the guanine nucleotide exchanging factor of Rac1. In fact, overexpression of dominant-negative form of Rac1 inhibits TCR-mediated activation of NFAT. Phosphorylation of Tyr446 recruits the SH2 domain of Lck for the optimal activation of transcription factors. Furthermore, point mutation of Arg486 in the 3BP2-SH2 domain that couples ZAP-70 to LAT dramatically reduces NFAT activation. These results suggest that the site-directed functions of 3BP2 induce the activation of transcription factors.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi048353o