Yustein J T, Li D, Robinson D, Kung H J
Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, Ohio 44106-4960, USA.
Oncogene. 2000 Feb 3;19(5):710-8. doi: 10.1038/sj.onc.1203342.
The Sterile-20 (Ste20) family of serine-threonine kinases has been implicated in the activation of the stress-activated protein kinase pathways. However, the physiological role has remained ambiguous for most of the investigated mammalian Ste20's. Here we report the cloning of a novel Ste20-like kinase, from chicken embryo fibroblast (CEF) cells, which we have named KFC, for Kinase From Chicken. The 898 amino acid full-length KFC protein contains an amino-terminal kinase domain, an adjacent downstream serine-rich region, and a C-terminal tail containing a coiled-coil domain. Here we show that the coiled-coil domain of KFC negatively regulates the intrinsic kinase activity. We have also identified a splice variant of KFC in which there is a 207 nucleotide in-frame deletion. This deletion of 69 amino acids encompasses the serine-rich region. These two isoforms, called KFCL, for full-length, and KFCS for spliced (or short) form, not only differ in structure, but also in biological properties. Stable CEF cells overexpressing KFCL, but not KFCS, have a significant increase in growth rate when compared to parental cells. This mitogenic effect is the first such reported for this family of kinases. Finally, we found that KFC, when activated by truncation of the regulatory C-terminus, has a specific activation of the stress-activated protein kinase (SAPK/JNK) pathway.
丝氨酸 - 苏氨酸激酶的无菌20（Ste20）家族与应激激活蛋白激酶途径的激活有关。然而，对于大多数已研究的哺乳动物Ste20来说，其生理作用仍不明确。在此，我们报告从鸡胚成纤维细胞（CEF）中克隆出一种新型的Ste20样激酶，我们将其命名为KFC，即来自鸡的激酶。898个氨基酸的全长KFC蛋白包含一个氨基末端激酶结构域、一个相邻的下游富含丝氨酸区域以及一个含有卷曲螺旋结构域的羧基末端尾巴。在此我们表明，KFC的卷曲螺旋结构域负向调节其内在激酶活性。我们还鉴定出KFC的一种剪接变体，其中存在一个207个核苷酸的框内缺失。这个69个氨基酸的缺失包含了富含丝氨酸的区域。这两种异构体，分别称为全长的KFCL和剪接（或短）形式的KFCS，不仅在结构上不同，而且在生物学特性上也不同。与亲代细胞相比，稳定过表达KFCL而非KFCS的CEF细胞生长速率显著增加。这种促有丝分裂作用是该激酶家族首次报道的此类作用。最后，我们发现，当通过截短调节性羧基末端激活KFC时，应激激活蛋白激酶（SAPK/JNK）途径会被特异性激活。
