Chai Biaoxin, Li Ji-Yao, Zhang Weizhen, Ammori John B, Mulholland Michael W
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Regul Pept. 2007 Mar 1;139(1-3):115-21. doi: 10.1016/j.regpep.2006.11.003. Epub 2006 Dec 22.
HEK 293 cells stably expressing human melanocortin-3 receptor (MC3R) were exposed to melanocortin receptor agonist, NDP-MSH (10(-)(10)-10(-)(6) M). ERK1/2 was phosphorylated in a dose-dependent manner with an EC(50) of 3.3+/-1.5 x 10(-)(9) M, similar to the IC(50) of NDP-MSH binding to the MC3R. ERK1/2 phosphorylation was blocked by the melanocortin receptor antagonists SHU9119. NDP-MSH-induced ERK1/2 phosphorylation was sensitive to pertussis toxin and the PI3K inhibitor, wortmannin. Rp-cAMPS, BAPTA-AM and Myr-PKC did not inhibit the NDP-MSH-induced ERK1/2 phosphorylation. NDP-MSH stimulated cellular proliferation in a dose-dependent manner with a similar EC(50) to ERK1/2 phosphorylation, 2.1+/-0.6 x 10(-)(9) M. Cellular proliferation was blocked by AGRP (86-132) and by the MEK inhibitor, PD98059. The NDP-MSH did not inhibit serum deprivation-induced apoptosis. MC3R activation induces ERK1/2 phosphorylation via PI3K and this pathway is involved in cellular proliferation in HEK cells expressing MC3R.
将稳定表达人促黑素皮质素-3受体（MC3R）的HEK 293细胞暴露于促黑素皮质素受体激动剂NDP-MSH（10⁻¹⁰ - 10⁻⁶ M）。ERK1/2以剂量依赖性方式磷酸化，EC₅₀为3.3±1.5×10⁻⁹ M，类似于NDP-MSH与MC3R结合的IC₅₀。ERK1/2磷酸化被促黑素皮质素受体拮抗剂SHU9119阻断。NDP-MSH诱导的ERK1/2磷酸化对百日咳毒素和PI3K抑制剂渥曼青霉素敏感。Rp-cAMPS、BAPTA-AM和Myr-PKC不抑制NDP-MSH诱导的ERK1/2磷酸化。NDP-MSH以剂量依赖性方式刺激细胞增殖，其EC₅₀与ERK1/2磷酸化相似，为2.1±0.6×10⁻⁹ M。细胞增殖被AGRP（86 - 132）和MEK抑制剂PD98059阻断。NDP-MSH不抑制血清剥夺诱导的细胞凋亡。MC3R激活通过PI3K诱导ERK1/2磷酸化，并且该途径参与表达MC3R的HEK细胞中的细胞增殖。
