PMID- 10068673
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 6
DP  - 1999 Mar 15
TI  - Involvement of wiskott-aldrich syndrome protein in B-cell cytoplasmic tyrosine
      kinase pathway.
PG  - 2003-12
AB  - Bruton's tyrosine kinase (Btk) has been shown to play a role in normal
      B-lymphocyte development. Defective expression of Btk leads to human and murine
      immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal
      transduction in B cells is still unclear. This study represents a search for the 
      substrate for Btk in vivo. We identified one of the major phosphoproteins
      associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome
      protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which 
      is another hereditary immunodeficiency with distinct abnormalities in
      hematopoietic cells. We demonstrated that WASP was transiently
      tyrosine-phosphorylated after B-cell antigen receptor cross-linking on B cells,
      suggesting that WASP is located downstream of cytoplasmic tyrosine kinases. An in
      vivo reconstitution system demonstrated that WASP is physically associated with
      Btk and can serve as the substrate for Btk. A protein binding assay suggested
      that the tyrosine-phosphorylation of WASP alters the association between WASP and
      a cellular protein. Furthermore, identification of the phosphorylation site of
      WASP in reconstituted cells allowed us to evaluate the catalytic specificity of
      Btk, the exact nature of which is still unknown.
FAU - Baba, Y
AU  - Baba Y
AD  - Department of Medicine III, Osaka University Medical School, Osaka, Japan.
FAU - Nonoyama, S
AU  - Nonoyama S
FAU - Matsushita, M
AU  - Matsushita M
FAU - Yamadori, T
AU  - Yamadori T
FAU - Hashimoto, S
AU  - Hashimoto S
FAU - Imai, K
AU  - Imai K
FAU - Arai, S
AU  - Arai S
FAU - Kunikata, T
AU  - Kunikata T
FAU - Kurimoto, M
AU  - Kurimoto M
FAU - Kurosaki, T
AU  - Kurosaki T
FAU - Ochs, H D
AU  - Ochs HD
FAU - Yata, J i
AU  - Yata Ji
FAU - Kishimoto, T
AU  - Kishimoto T
FAU - Tsukada, S
AU  - Tsukada S
LA  - eng
GR  - HD17427/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (WAS protein, human)
RN  - 0 (Wiskott-Aldrich Syndrome Protein)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
RN  - EC 2.7.10.2 (BTK protein, human)
SB  - AIM
SB  - IM
MH  - Agammaglobulinaemia Tyrosine Kinase
MH  - Amino Acid Sequence
MH  - Animals
MH  - B-Lymphocytes/*enzymology
MH  - Binding Sites
MH  - Burkitt Lymphoma
MH  - Cross-Linking Reagents
MH  - Cytoplasm/enzymology
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protein-Tyrosine Kinases/chemistry/genetics/*metabolism
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Receptors, Antigen, B-Cell/metabolism
MH  - Structure-Activity Relationship
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Wiskott-Aldrich Syndrome Protein
EDAT- 1999/03/09 00:00
MHDA- 1999/03/09 00:01
CRDT- 1999/03/09 00:00
PHST- 1999/03/09 00:00 [pubmed]
PHST- 1999/03/09 00:01 [medline]
PHST- 1999/03/09 00:00 [entrez]
AID - S0006-4971(20)48675-6 [pii]
PST - ppublish
SO  - Blood. 1999 Mar 15;93(6):2003-12.