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  • Original Paper
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Comparative studies of a new subfamily of human Ste20-like kinases: homodimerization, subcellular localization, and selective activation of MKK3 and p38

Oncogene volume 22, pages 6129–6141 (2003)Cite this article

Abstract

The Sterile-20 or Ste20 family of serine/threonine kinases is a group of signaling molecules whose physiological roles within mammalian cells are just starting to be elucidated. Here, in this report we present the characterization of three human Ste20-like kinases with greater than 90% similarity within their catalytic domains that define a novel subfamily of Ste20s. Members of this kinase family include rat thousand and one (TAO1) and chicken KFC (kinase from chicken). For the lack of a consensus nomenclature in the literature, in this report, we shall call this family hKFC (for their homology to chicken KFC) and the three members hKFC-A, hKFC-B, and hKFC-C, respectively. These kinases have many similarities including an aminoterminal kinase domain, a serine-rich region, and a coiled-coil configuration within the C-terminus. All three kinases are able to activate the p38 MAP kinase pathway through the specific activation of the upstream MKK3 kinase. We also offer evidence, both theoretical and biochemical, showing that these kinases can undergo self-association. Despite these similarities, these kinases differ in tissue distribution, apparent subcellular localization, and feature structural differences largely within the carboxyl-terminal sequence.

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Abbreviations

ASK1:

apoptosis signal-regulating kinase 1

CRIB:

Cdc42/Rac1 interactive-binding domain

EGF:

epidermal growth factor

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

FITC:

fluorescein isothiocyanate

GCK:

germinal center kinase

GST:

glutathione S-transferase

HA:

hemagglutinin

HRP:

horseradish peroxidase

IL-1β:

interleukin-1β

KFC:

kinase from chicken

LFA:

leukocyte-function-associated antigen

MAPK:

mitogen-activated protein kinase

MBP:

myelin basic protein

MEK/MKK:

MAPK kinase

MEKK:

MEK-kinase

MLK:

mixed-lineage kinase

MST1:

mammalian Ste20

MTK1:

MAP three kinase 1

p38/mHOG:

mammalian high-osmolarity glycerol kinase

PAGE:

polyacrylamide gel electrophoresis

PAK:

p21-activated kinase

PBL:

peripheral blood leukocytes

PDGF:

platelet-derived growth factor

PSK:

prostate-specific kinase

RACE:

rapid amplification of cDNA ends

SAPK/JNK:

stress-activated protein kinase/jun N-terminal kinase

SH3:

src-homology 3

Ste20:

sterile-20

TAK1:

TGF-β-activated kinase 1

TAO1:

thousand and one protein kinase

TGF-β:

transforming growth factor-β

TNF-α:

tumor necrosis factor-α

UV:

ultraviolet

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Acknowledgements

We thank Dr Ichijo (Tokyo Medical and Dental University) for providing the HA-tagged ASK1 clone. This work is supported by NIH grants (CA39207, CA46613 and CA57179) and a DOD prostate cancer grant (DAMD17-02-1-0020) to HJK JTY is supported through the NIH-supported Medical Scientist Training Program. We also acknowledge the support of Cancer Center Core Grant to UC Davis and the Environmental Health Science Center Grant to UC Davis.

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Authors and Affiliations

  1. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, 44106-4960, OH, USA

    Jason T Yustein

  2. University of California at Davis Cancer Center, UCDMC, Res. III, 4645 2nd Avenue, Sacramento, 95817, CA, USA

    Liang Xia, Dan Robinson & Hsing-Jien Kung

  3. Department of Pathology, Case Western Reserve University, Cleveland, 44106, OH, USA

    J Michelle Kahlenburg

  4. Department of Pathology, University of Virginia, Charlottesville, 22908, VA, USA

    Dennis Templeton

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Correspondence to Hsing-Jien Kung.

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Yustein, J., Xia, L., Kahlenburg, J. et al. Comparative studies of a new subfamily of human Ste20-like kinases: homodimerization, subcellular localization, and selective activation of MKK3 and p38. Oncogene 22, 6129–6141 (2003). https://doi.org/10.1038/sj.onc.1206605

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