Regulation of id gene expression by type I insulin-like growth factor: Roles of STAT3 and the tyrosine 950 residue of the receptor

Id proteins are known to play important roles in the proliferation and diff erentiation of many cell types. The type 1 insulin-like growth factor recep tor (IGF-IR), activated by its ligand, induces the differentiation of 32D I GF-IR cells, a murine hematopoietic cell line, expressing a human IGF-IR. E xpression in 32D IGF-IR cells of a dominant negative mutant or Stat3 (DNSta t3) inhibits IGF-I-mediated differentiation. DNStat3 causes a dramatic incr ease in Id2 gene expression. This increase, however, is IGF-I dependent and is abrogated by a mutation at tyrosine 950 of the IGF-IR. These results in dicate that in 32D cells, the IGF-IR regulates the expression of the Id2 ge ne and that this regulation is modulated by both positive and negative sign als. Our results also suggest that in this model, Id2 proteins influence th e differentiation program of cells but are not sufficient for the full stim ulation of their proliferation program.