INTERLEUKIN-5 SIGNALS THROUGH SHC AND GRB2 IN HUMAN EOSINOPHILS

Citation
Me. Bates et al., INTERLEUKIN-5 SIGNALS THROUGH SHC AND GRB2 IN HUMAN EOSINOPHILS, American journal of respiratory cell and molecular biology, 18(1), 1998, pp. 75-83
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology",Biology,"Respiratory System
ISSN journal
1044-1549
Volume
18
Issue
1
Year of publication
1998
Pages
75 - 83
Database
ISI
SICI code
1044-1549(1998)18:1<75:ISTSAG>2.0.ZU;2-U
Abstract
Eosinophils are potent effector cells contributing to allergic inflamm ation and asthma. The differentiation, recruitment, and effector funct ions of eosinophils are greatly affected by interleukin (IL)-5. In the eosinophil, signal transduction pathways including Jak-STAT and Ras-R af-MAP kinase are stimulated by IL-5 and enzymatic activation of tyros ine kinases Jak-2 and Lyn has been demonstrated, The participation of adapter proteins in the responses of the Ras-Raf-MAP kinase pathway ha s been documented in many cytokine family receptors but the expression and activation of these proteins have not been demonstrated in eosino phils. In these studies, we have found three isoforms of the adapter p rotein, Shc, to be expressed in eosinophils. One of these isoforms, p5 2 Shc, was tyrosine phosphorylated following IL-5 treatment of eosinop hils. A second adapter protein, Grb2, coimmunoprecipitated with Shc fo llowing IL-5 stimulation of eosinophils. Furthermore, p52 Shc was incr easingly associated with a cell fraction resistant to detergent solubi lization, following IL-5 administration. This cell fraction of limited detergent solubility is a complex mixture of proteins and the adapter protein Grb2, the tyrosine kinases Jak-2 and Lyn, the nucleotide exch ange factor Vav, and the serine-threonine kinases p45 MAP kinase, Raf- 1, and PKC beta, were distributed either wholly or partially in the sa me fraction, as were the cytoskeletal proteins actin and vimentin. Onl y p52 Shc, however, demonstrated discernibly increased association wit h this fraction following IL-5 stimulation of eosinophils. These data suggest that IL-5 activates a signal transduction pathway utilizing th e adapter proteins Shc and Grb2 in the human eosinophil.