KFC, a Ste20-like kinase with mitogenic potential and capability to activate the SAPK/JNK pathway
J T Yustein1, D Li, D Robinson
1Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, Ohio 44106-4960, USA.
Oncogene
|March 4, 2000
Summary
We identified a novel kinase, Kinase From Chicken (KFC), and its splice variant. The full-length KFC isoform promotes cell growth, while activated KFC specifically activates the stress-activated protein kinase pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The Sterile-20 (Ste20) kinase family plays a role in stress-activated protein kinase pathways.
- The physiological functions of most mammalian Ste20 kinases remain unclear.
Purpose of the Study:
- To clone and characterize a novel Ste20-like kinase from chicken embryo fibroblast (CEF) cells.
- To investigate the structure, function, and biological properties of the novel kinase and its isoforms.
Main Methods:
- Cloning of the novel Ste20-like kinase, named KFC (Kinase From Chicken).
- Identification and characterization of a KFC splice variant (KFCS).
- Analysis of kinase activity regulation and cellular effects of KFC isoforms.
Main Results:
- The full-length KFC protein (KFCL) has a kinase domain, serine-rich region, and a C-terminal coiled-coil domain that negatively regulates activity.
- A splice variant, KFCS, lacks the serine-rich region.
- Overexpression of KFCL, but not KFCS, significantly increases CEF cell growth rate, representing a novel mitogenic effect for this kinase family.
- Activated KFC specifically activates the stress-activated protein kinase (SAPK/JNK) pathway.
Conclusions:
- KFC is a novel Ste20-like kinase with distinct isoforms (KFCL and KFCS) possessing different biological properties.
- KFCL exhibits a unique mitogenic effect, promoting cell proliferation.
- KFC activation leads to specific activation of the SAPK/JNK pathway, highlighting its role in cellular signaling.
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