Bassing C H, Shou W, Muir S, Heitman J, Matzuk M M, Wang X F
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cell Growth Differ. 1998 Mar;9(3):223-8.
Transforming growth factor beta (TGF-beta) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF-beta signaling in mink lung epithelial cells, and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-beta receptor I interaction, we investigated whether disruption of this interaction affects TGF-beta-signaling in primary mouse embryo fibroblasts and thymocytes. We found that the addition of excess drugs had no effect on either TGF-beta-mediated transcriptional responses or growth inhibition. Dose-response curves for TGF-beta-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12-deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-beta signaling in primary fibroblasts and thymocytes.
转化生长因子β（TGF-β）通过I型和II型跨膜丝氨酸 - 苏氨酸激酶的异源复合物进行信号传导。最近的证据表明，免疫亲和素FKBP12调节I型受体的活性，这是基于以下数据：破坏FKBP12与I型受体结合的免疫抑制药物可增强水貂肺上皮细胞中的TGF-β信号传导，并且FKBP12的过表达会抑制II型受体对I型受体的磷酸化作用。为了确定FKBP12与TGF-β受体I相互作用的生理相关性，我们研究了这种相互作用的破坏是否会影响原代小鼠胚胎成纤维细胞和胸腺细胞中的TGF-β信号传导。我们发现添加过量药物对TGF-β介导的转录反应或生长抑制均无影响。从野生型或FKBP12缺陷型小鼠分离的原代成纤维细胞和胸腺细胞中，TGF-β介导的信号传导的剂量反应曲线是相同的。综上所述，我们的结果表明FKBP12在原代成纤维细胞和胸腺细胞的TGF-β信号传导中不发挥独特的生理作用。
