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
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.