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 differentiation of many cell types. The type 1 insulin-like growth factor receptor (IGF-IR), activated by its ligand, induces the differentiation of 32D IGF-IR cells, a murine hematopoietic cell line, expressing a human IGF-IR. Expression in 32D IGF-IR cells of a dominant negative mutant of Stat3 (DNStat3) inhibits IGF-I-mediated differentiation. DNStat3 causes a dramatic increase 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 indicate that in 32D cells, the IGF-IR regulates the expression of the Id2 gene and that this regulation is modulated by both positive and negative signals. Our results also suggest that in this model, Id2 proteins influence the differentiation program of cells but are not sufficient for the full stimulation of their proliferation program.

已知Id蛋白（Id proteins）在多种细胞类型的增殖与分化进程中发挥重要调控功能。胰岛素样生长因子1型受体（type 1 insulin-like growth factor receptor, IGF-IR）经其配体激活后，可诱导表达人源IGF-IR的小鼠造血细胞系32D IGF-IR细胞产生分化。在32D IGF-IR细胞中过表达Stat3显性负性突变体（dominant negative mutant of Stat3, DNStat3），可抑制胰岛素样生长因子I（IGF-I）介导的细胞分化。该显性负性突变体可显著上调Id2基因的表达水平，但该表达上调依赖于IGF-I信号，且可被IGF-IR酪氨酸950位点的突变所阻断。上述结果表明，在32D细胞中，IGF-IR可调控Id2基因的表达，且该调控过程受到正负双向信号的协同调节。本研究结果同时提示，在该细胞模型中，Id2蛋白可影响细胞的分化程序，但不足以完全激活细胞的增殖程序。