Insulin-like Growth Factor I Receptor Signaling in Differentiation of Neuronal H19-7 Cells
2000
The type I insulin-like growth factor receptor (IGF-IR) is known to send
two seemingly contradictory signals inducing either cell proliferation
or cell differentiation, depending on cell type and/or conditions.
H19-7 cells are rat hippocampal neuronal cells immortalized by a
temperature-sensitive SV40 large T antigen that grow at 34°C in
epidermal growth factor or serum but differentiate at 39°C when
induced by basic fibroblast growth factor. At 39°C, expression of the
human IGF-IR in H19-7 cells induces an insulin-like growth factor (IGF)
I-dependent differentiation. We have investigated the domains of the
IGF-IR required for differentiation of H19-7 cells. The tyrosine 950
residue and serines 1280–1283 in the COOH terminus of the receptor are
required for IGF-I-induced differentiation at 39°C, although they are
dispensable for IGF-I-mediated growth at 34°C. Both domains have to
be mutated to inactivate the differentiating function. The inability of
these mutant receptors to induce differentiation correlates with
mitogen-activated protein kinase activation. In contrast, inhibitors of
phosphatidylinositol 3′-kinase have no effect on IGF-I-mediated
differentiation of H19-7 cells, although they do inhibit the mitogenic
response.
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