Hemesath T J, Price E R, Takemoto C, Badalian T, Fisher D E
Division of Pediatric Hematology/Oncology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1998 Jan 15;391(6664):298-301. doi: 10.1038/34681.
Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (S1) result in strikingly similar defects in mast cell and melanocyte development. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with S1 results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus.
编码转录因子小眼畸形（Mi）、细胞因子受体c-Kit或其配体Steel因子（S1）的基因座发生种系突变，会在肥大细胞和黑素细胞发育过程中导致极为相似的缺陷。在此，我们描述了Kit信号传导与Mi活性之间的生化联系。用S1刺激黑素瘤细胞会导致丝裂原活化蛋白激酶（MAP激酶）激活，进而使Mi在一个共有靶丝氨酸处磷酸化。这种磷酸化上调了Mi对酪氨酸酶色素沉着基因启动子的反式激活作用。除了调节色素生成外，此类信号传导可能还会调节黑素细胞存活和发育所必需的基因的表达。该信号通路代表了通用MAP激酶机制在转导细胞表面组织特异性受体与细胞核内组织特异性转录因子之间信号方面的一种新应用。
