Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States.
Department of Pediatrics, Division of Allergy, Asthma, and Immunology, Children's Mercy Hospital, Kansas City, MO, United States.
Immunobiology. 2021 Mar;226(2):152067. doi: 10.1016/j.imbio.2021.152067. Epub 2021 Jan 28.
We examined signaling differences between two co-stimulatory molecules, CD28 and ICAM-1 by analyzing transcription factors and proteins that are activated downstream of these co-stimulations. We observed that FAST-1, a crucial protein in the TGFβ signaling pathway, was activated by only ICAM-1 co-stimulation, and not by CD28. We also observed that receptor tyrosine kinases Csk, Dtk, FGFR1 and ROR2 were phosphorylated upon CD28 co-stimulation and IGF-1R, HGFR, MuSK and EphA8 were phosphorylated upon ICAM-1 co-stimulation. Together, these findings suggest that these two co-stimulators induce the activation of different sets of proteins, suggesting that each co-stimulatory molecule has its unique signaling profile.
我们通过分析这两种共刺激分子(CD28 和 ICAM-1)下游激活的转录因子和蛋白,研究了它们之间信号通路的差异。我们发现,FAST-1 是 TGFβ 信号通路中的关键蛋白,仅能被 ICAM-1 共刺激激活,而不能被 CD28 激活。我们还观察到,受体酪氨酸激酶 Csk、Dtk、FGFR1 和 ROR2 在 CD28 共刺激下发生磷酸化,而 IGF-1R、HGFR、MuSK 和 EphA8 在 ICAM-1 共刺激下发生磷酸化。这些结果表明,这两种共刺激分子诱导了不同蛋白集的激活,提示每种共刺激分子都有其独特的信号通路特征。