Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling

S Hashimoto; A Iwamatsu; M Ishiai; K Okawa; T Yamadori; M Matsushita; Y Baba; T Kishimoto; T Kurosaki; S Tsukada

Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling

Blood. 1999 Oct 1;94(7):2357-64.

Authors

S Hashimoto¹, A Iwamatsu, M Ishiai, K Okawa, T Yamadori, M Matsushita, Y Baba, T Kishimoto, T Kurosaki, S Tsukada

Affiliation

¹ Department of Molecular Medicine, Osaka University Medical School, Osaka, Japan.

PMID: 10498607

Abstract

Bruton's tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling. It is known that this BCR-induced calcium signaling depends on the activation of phospholipase Cgamma (PLCgamma), which is mediated by Btk and another tyrosine kinase Syk and that the SH2 and pleckstrin homology (PH) domains of Btk play important roles in this activation process. Although the importance of the PH domain of Btk has been explained by its role in the membrane targeting of Btk, the functional significance of the SH2 domain in the calcium signaling has remained merely a matter of speculation. In this report, we identify that one of the major Btk-SH2 domain-binding proteins in B cells is BLNK (B-cell linker protein) and present evidences that the interaction of BLNK and the SH2 domain of Btk contributes to the complete tyrosine phosphorylation of PLCgamma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agammaglobulinaemia Tyrosine Kinase
Amino Acid Sequence
Amino Acid Substitution
Burkitt Lymphoma
Calcium / physiology*
Enzyme Precursors / metabolism
Humans
Intracellular Signaling Peptides and Proteins
Isoenzymes / metabolism
Molecular Sequence Data
Mutagenesis, Site-Directed
Peptide Fragments / chemistry
Phospholipase C gamma
Protein-Tyrosine Kinases / chemistry*
Protein-Tyrosine Kinases / metabolism*
Receptors, Antigen, T-Cell / immunology*
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / metabolism
Serine Endopeptidases
Signal Transduction
Syk Kinase
Transfection
Tumor Cells, Cultured
Type C Phospholipases / metabolism
src Homology Domains

Substances

Enzyme Precursors
Intracellular Signaling Peptides and Proteins
Isoenzymes
Peptide Fragments
Receptors, Antigen, T-Cell
Recombinant Fusion Proteins
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
BTK protein, human
SYK protein, human
Syk Kinase
Type C Phospholipases
Phospholipase C gamma
Serine Endopeptidases
lysyl endopeptidase
Calcium