TY - JOUR
T1 - KFC, a Ste20-like kinase with mitogenic potential and capability to activate the SAPK/JNK pathway
AU - Yustein, Jason T.
AU - Li, Deshan
AU - Robinson, Dan
AU - Kung, Hsing Jien
N1 - Funding Information:
We would like to thank Dr Dennis Templeton for pEBG ERK1, SAPK-b, and p38/mHOG constructs, as well as providing the MEKK WT construct used. We also thank Dr Lucy Lee (Michigan State University) for providing us with additional chicken tissues. This work is supported by NIH grants (CA39207, CA46613 and CA57179) to HJ Kung. JT Yustein is supported through the NIH supported Medical Scientist Training Program.
PY - 2000/2/3
Y1 - 2000/2/3
N2 - 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.
AB - 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.
KW - Chicken embryo fibroblast
KW - KFC
KW - Mitogenesis
KW - SAPK/JNK
KW - Ste20
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U2 - 10.1038/sj.onc.1203342
DO - 10.1038/sj.onc.1203342
M3 - Article
C2 - 10698516
AN - SCOPUS:0034598814
SN - 0950-9232
VL - 19
SP - 710
EP - 718
JO - Oncogene
JF - Oncogene
IS - 5
ER -