Takada K, Tada H, Takano T, Nishiyama S, Amino N
Department of Laboratory Medicine, Osaka University Medical School, Japan.
FEBS Lett. 1993 Mar 8;318(3):245-8. doi: 10.1016/0014-5793(93)80521-u.
The regulatory effects of lithium on the function of pertussis toxin-sensitive GTP-binding (G(i))-proteins located on the mitogenic pathway activated by insulin-like growth factor-I (IGF-I) in FRTL-5 cells were studied. Addition of GTP-gamma-S to the thyroid stimulating hormone-primed cell membranes resulted in a decreased affinity of IGF-I receptor binding, and the dissociation constant (Kd) increased from 0.46 nM to 3.1 nM. Moreover, IGF-I stimulated GTP-gamma-S binding to a 40-kDa protein, and pertussis toxin (PT) attenuated the stimulatory effect of IGF-I on the same protein. Lithium lowered the affinity of IGF-I receptor binding and the Kd (3.4 nM) was in the same range as that in the presence of GTP-gamma-S. The inhibitory effect of lithium was markedly abolished by pretreatment with PT. Lithium attenuated the amounts of ADP-rebosylation of the 40-kDa protein by PT. In addition, lithium stimulated Ca2+ entry, similar to that by IGF-I, and induced cell proliferation via a PT-sensitive step. These findings suggest that lithium may be capable of modulating the function of G(i)-proteins coupled to IGF-I receptors during the G1 phase of the FRTL-5 cell cycle.
研究了锂对FRTL-5细胞中位于胰岛素样生长因子-I（IGF-I）激活的促有丝分裂途径上的百日咳毒素敏感型GTP结合（G(i)）蛋白功能的调节作用。向促甲状腺激素预处理的细胞膜中添加GTP-γ-S导致IGF-I受体结合亲和力降低，解离常数（Kd）从0.46 nM增加到3.1 nM。此外，IGF-I刺激GTP-γ-S与一种40 kDa蛋白结合，而百日咳毒素（PT）减弱了IGF-I对同一蛋白的刺激作用。锂降低了IGF-I受体结合亲和力，Kd（3.4 nM）与存在GTP-γ-S时处于同一范围。锂的抑制作用通过PT预处理明显消除。锂减弱了PT对40 kDa蛋白的ADP-核糖基化量。此外，锂刺激Ca2+内流，类似于IGF-I，并通过PT敏感步骤诱导细胞增殖。这些发现表明，锂可能能够在FRTL-5细胞周期的G1期调节与IGF-I受体偶联的G(i)蛋白的功能。
