Your browser doesn't support javascript.
loading
Tec kinases mediate sustained calcium influx via site-specific tyrosine phosphorylation of the phospholipase Cgamma Src homology 2-Src homology 3 linker.
Humphries, Lisa A; Dangelmaier, Carol; Sommer, Karen; Kipp, Kevin; Kato, Roberta M; Griffith, Natasha; Bakman, Irene; Turk, Christoph W; Daniel, James L; Rawlings, David J.
Afiliação
  • Humphries LA; Molecular Biology Institute and Department of Microbiology and Immunology, UCLA, Los Angeles, California 90095, USA.
J Biol Chem ; 279(36): 37651-61, 2004 Sep 03.
Article em En | MEDLINE | ID: mdl-15184383
ABSTRACT
Tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2) is a crucial activation switch that initiates and maintains intracellular calcium mobilization in response to B cell antigen receptor (BCR) engagement. Although members from three distinct families of non-receptor tyrosine kinases can phosphorylate PLCgamma in vitro, the specific kinase(s) controlling BCR-dependent PLCgamma activation in vivo remains unknown. Bruton's tyrosine kinase (Btk)-deficient human B cells exhibit diminished inositol 1,4,5-trisphosphate production and calcium signaling despite a normal inducible level of total PLCgamma2 tyrosine phosphorylation. This suggested that Btk might modify a critical subset of residues essential for PLCgamma2 activity. To evaluate this hypothesis, we generated site-specific phosphotyrosine antibodies recognizing four putative regulatory residues within PLCgamma2. Whereas all four sites were rapidly modified in response to BCR engagement in normal B cells, Btk-deficient B cells exhibited a marked reduction in phosphorylation of the Src homology 2 (SH2)-SH3 linker region sites, Tyr(753) and Tyr(759). Phosphorylation of both sites was restored by expression of Tec, but not Syk, family kinases. In contrast, phosphorylation of the PLCgamma2 carboxyl-terminal sites, Tyr(1197) and Tyr(1217), was unaffected by the absence of functional Btk. Together, these data support a model whereby Btk/Tec kinases control sustained calcium signaling via site-specific phosphorylation of key residues within the PLCgamma2 SH2-SH3 linker.
Assuntos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Fosfolipases Tipo C / Tirosina / Proteínas Tirosina Quinases / Cálcio Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2004 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Fosfolipases Tipo C / Tirosina / Proteínas Tirosina Quinases / Cálcio Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2004 Tipo de documento: Article