Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 710-718 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 19 |
Issue number | 5 |
State | Published - Feb 3 2000 |
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Keywords
- Chicken embryo fibroblast
- KFC
- Mitogenesis
- SAPK/JNK
- Ste20
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
KFC, a Ste20-like kinase with mitogenic potential and capability to activate the SAPK/JNK pathway. / Yustein, Jason T.; Li, Deshan; Robinson, Dan; Kung, Hsing-Jien.
In: Oncogene, Vol. 19, No. 5, 03.02.2000, p. 710-718.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=0034598814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034598814&partnerID=8YFLogxK
M3 - Article
C2 - 10698516
AN - SCOPUS:0034598814
VL - 19
SP - 710
EP - 718
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 5
ER -