| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and Formyl-Methionyl-Leucyl-Phenylalanine Receptors in Differentiated THP-1 Cells 1
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
The class Ia phosphoinositide (PI) 3-kinase consisting of p110 catalytic and p85 regulatory subunits is activated by Tyr kinase-linked membrane receptors such as Fc
RII through the association of p85 with the phosphorylated receptors or adaptors. The heterodimeric PI 3-kinase is also activated by G protein-coupled chemotactic fMLP receptors, and activation of the lipid kinase plays an important role in various immune responses, including superoxide formation in neutrophils. Although fMLP-induced superoxide formation is markedly enhanced in FcRII-primed neutrophils, the molecular mechanisms remain poorly characterized. In this study, we identified two Tyr-phosphorylated proteins, c-Cbl (Casitas B-lineage lymphoma) and Grb2-associated binder 2 (Gab2), as PI 3-kinase adaptors that are Tyr phosphorylated upon the stimulation of FcRII in differentiated neutrophil-like THP-1 cells. Interestingly, Gab2 was, but c-Cbl was not, further Ser/Thr phosphorylated by fMLP. Thus, the adaptor Gab2 appeared to be dually phosphorylated at the Ser/Thr and Tyr residues through the two different types of membrane receptors. The Ser/Thr phosphorylation of Gab2 required the activation of extracellular signal-regulated kinase, and fMLP receptor stimulation indeed activated extracellular signal-regulated kinase in the cells. Enhanced superoxide formation in response to Fc and fMLP was markedly attenuated when the Gab2 Ser/Thr phosphorylation was inhibited. These results show the importance of the dual phosphorylation of PI 3-kinase adaptor Gab2 for the enhanced superoxide formation in neutrophil-type cells.
This article has been cited by other articles:
|
|
 |
|
  H. Ikeda, H. Okazawa, H. Ohnishi, Y. Murata, P.-A. Oldenborg, and T. Matozaki Mutational analysis of the mechanism of negative regulation by SRC homology 2 domain-containing protein tyrosine phosphatase substrate-1 of phagocytosis in macrophages. J. Immunol., September 1, 2006; 177(5): 3123 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Condliffe, K. Davidson, K. E. Anderson, C. D. Ellson, T. Crabbe, K. Okkenhaug, B. Vanhaesebroeck, M. Turner, L. Webb, M. P. Wymann, et al. Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils Blood, August 15, 2005; 106(4): 1432 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. T. Wu and Y. H. Wong Involvement of Gi/o Proteins in Nerve Growth Factor-Stimulated Phosphorylation and Degradation of Tuberin in PC-12 Cells and Cortical Neurons Mol. Pharmacol., April 1, 2005; 67(4): 1195 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Okazawa, S.-i. Motegi, N. Ohyama, H. Ohnishi, T. Tomizawa, Y. Kaneko, P.-A. Oldenborg, O. Ishikawa, and T. Matozaki Negative Regulation of Phagocytosis in Macrophages by the CD47-SHPS-1 System J. Immunol., February 15, 2005; 174(4): 2004 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Kim, S. C. Chu, J. L. Gramlich, Y. B. Pride, E. Babendreier, D. Chauhan, R. Salgia, K. Podar, J. D. Griffin, and M. Sattler Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species Blood, February 15, 2005; 105(4): 1717 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Brandes and J. Kreuzer Vascular NADPH oxidases: molecular mechanisms of activation Cardiovasc Res, January 1, 2005; 65(1): 16 - 27. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
