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Insulin-like
growth factor I receptor signaling in differentiation of neuronal H19-7 cells
Morrione A, Romano G, Navarro M, Reiss K, Valentinis B, Dews M, Eves
E, Rosner MR, Baserga R
Kimmel Cancer
Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
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 degrees C in
epidermal growth factor or serum but differentiate at 39 degrees C when induced
by basic fibroblast growth factor.
At 39 degrees 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 degrees C,
although they are dispensable for IGF-I-mediated growth at 34 degrees 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.
PMID: 10786694 [PubMed - indexed for MEDLINE]
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