LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck

EMBO J. 1995 Jul 17;14(14):3403-14.

Abstract

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.

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptides / metabolism
  • Proline / metabolism*
  • Proline-Rich Protein Domains
  • Protein Conformation
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Complementary
  • DNA-Binding Proteins
  • Hcls1 protein, mouse
  • Peptides
  • Receptors, Antigen, T-Cell
  • Proline
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

Associated data

  • GENBANK/X84797