Takemoto Y, Furuta M, Li XK, Strong-Sparks WJ, Hashimoto Y.
LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck.
The Lck tyrosine kinase molecule plays an essential role in T cell activation and T cell development. Using the expression cloning technique, we have isolated a gene that encodes a molecule, LckBP1, able to associate with murine Lck. Analysis of full-length LckBP1 cDNA indicates at least four potentially important segments: a four tandem 37 amino acid repeat motif with a potential helix-turn-helix DNA binding motif; a proline-rich region; a proline-glutamate repeat; and an SH3 domain. These four regions are very similar to the human haematopoietic-specific protein 1 (HS1). Deletion mutant analysis of LckBP1 revealed two proline-rich regions that permit association with Lck SH3. One region contains prolines conserved among HS1 and cortactin, and the other region contains a potential MAP kinase recognition site. In vivo association between Lck and LckBP1 was confirmed by immunoprecipitation of lysates from a pre-T cell line and adult thymocytes using antibodies specific for Lck and LckBP1. LckBP1 is tyrosine phosphorylated after T-cell receptor stimulation. The SH3 domain and the potential helix-turn-helix motif in LckBP1 suggest that this molecule may associate with various molecules and function as a DNA binding molecule. The data also suggest that LckBP1 mediates intracellular signalling through Lck in T cells.
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism*
Hematopoietic Stem Cells / metabolism*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Mice, Inbred BALB C
Molecular Sequence Data
Peptides / metabolism
Proline / metabolism*
Proline-Rich Protein Domains
Protein-Tyrosine Kinases / metabolism*
Receptors, Antigen, T-Cell / metabolism
Sequence Homology, Amino Acid
T-Lymphocytes / metabolism
BIOCHEMISTRY & MOLECULAR BIOLOGY
Mouse HS1 (RDB01790)
GST-Lck SH3 (RDB02115)
GST-Lck SH2 (RDB02116)
GST-Lck SH32 (RDB02117)
GST-Lck Kinase (RDB02118)
KKF cDNA library (RDB02148).