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SPAK, a STE20/SPS1-related kinase that activates the p38 pathway

Oncogene volume 19, pages 4290–4297 (2000)Cite this article

Abstract

We have cloned a member of the STE20/SPS1 protein kinase family from a transformed rat pancreatic beta cell line. SPAK (STE20/SPS1-related, proline alanine-rich kinase) belongs to the SPS1 subfamily of STE20 kinases and is highly conserved between species. SPAK is expressed ubiquitously, although preferentially in brain and pancreas. Biochemical characterization of SPAK catalytic activity demonstrates that is a serine/threonine kinase that can phosphorylate itself and an exogenous substrate in vitro. SPAK is immunoprecipitated from transfected mammalian cells as a complex with another, as yet uncharacterized, serine/threonine kinase which is capable of phosphorylating catalytically-inactive SPAK and myelin basic protein in an in vitro kinase assay. SPAK specifically activates the p38 pathway in cotransfection assays. Like MST1 and MST2, SPAK contains a putative caspase cleavage site at the junction of the catalytic domain and the C-terminal region. Full-length SPAK is expressed in the cytoplasm in transfected cells, while a mutant corresponding to caspase-cleaved SPAK is expressed predominantly in the nucleus. The similarity of SPAK to other SPS1 family members, its ability to activate the p38 pathway, in addition to its putative caspase cleavage site, provide evidence that SPAK may act as a novel mediator of stress-activated signals.

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Abbreviations

MAP kinase:

mitogen activated protein kinase

ERK:

extracellular signal-regulated kinase

JNK:

c-Jun N terminal kinase

MAPKK:

mitogen activated protein kinase kinase

MAPKKK:

mitogen activated protein kinase kinase kinase

PAK:

p21-activated kinase

GCK:

germinal center kinase

GCKR:

germinal center kinase-related

GLK:

GCK-like kinase

HPK1:

hematopoietic progenitor kinase 1

NIK:

NCK-interacting kinase

SOK-1:

STE20/ oxidant stress responsive kinase-1

MST:

mammalian sterile 20-like

LOK:

lymphocyte oriented kinase

SPAK:

STE20/SPS1-related proline alanine-rich kinase

RIN:

rat insulinoma

BLAST:

basic local alignment search tool

GFP:

green fluorescent protein

PCR:

polymerase chain reaction

GST:

glutathione S-transferase

HA:

hemagglutinin

FCS:

fetal calf serum

IPTG:

isopropyl-B-D-thiogalactoside

DTT:

dithiothreitol

PMSF:

phenylmethylsulfonyl fluoride

MBP:

myelin basic protein

HRP:

horseradish peroxidase

TBS:

tris-buffered saline

PVDF:

polyvinylidene difluoride

References

  • Boulikas T. . 1993 Crit. Rev. Euk. Gene. Exp. 3: 193–227.

  • Brown JL, Stowers L, Baer M, Trejo J, Coughlin S and Chant J. . 1996 Curr. Biol. 6: 598–605.

  • Cahill MA, Peter ME, Kischkel FC, Chinnaiyan AM, Dixit VM, Krammer PH and Nordheim A. . 1996 Oncogene 13: 2087–2096.

  • Creasy CL and Chernoff J. . 1995a J. Biol. Chem. 270: 21695–21700.

  • Creasy CL and Chernoff J. . 1995b Gene. 167: 303–306.

  • DeAizpurua HJ, Cram DS, Naselli G, Devereux L and Dorow DS. . 1997 J. Biol. Chem. 272: 16364–16373.

  • Diener K, Wang XS, Chen C, Meyer CF, Keesler G, Zukowski M, Tan TH and Yao Z. . 1997 Proc. Natl. Acad. Sci. USA 94: 9687–9692.

  • Eichinger L, Bahler M, Dietz M, Eckerskorn C and Schleicher M. . 1998 J. Biol. Chem. 273: 12952–12959.

  • Frank G and Weeds AG. . 1974 Eur. J. Biochem. 44: 317–334.

  • Friesen H, Lunz R, Doyle S and Segall J. . 1994 Genes Dev. 8: 2162–2175.

  • Graves JD, Draves KE, Craxton A, Saklatvala J, Krebs EG and Clark EA. . 1996 Proc. Natl. Acad. Sci. USA 93: 13814–13818.

  • Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA and Krebs EG. . 1998 EMBO J. 17: 2224–2234.

  • Hejtmancik JF, Thompson MA, Wistow G and Piatigorsky J. . 1986 J. Biol. Chem. 261: 982–987.

  • Hu MC, Qiu WR, Wang X, Meyer CF and Tan TH. . 1996 Genes. Dev. 10: 2251–2264.

  • Juo P, Kuo CJ, Reynolds SE, Konz RF, Raingeaud J, Davis RJ, Biemann HP and Blenis J. . 1997 Mol. Cell. Biol. 17: 24–35.

  • Katz P, Whalen G and Kehrl JH. . 1994 J. Biol. Chem. 269: 16802–16809.

  • Kiefer F, Tibbles LA, Anafi M, Janssen A, Zanke BW, Lassam N, Pawson T, Woodgett JR and Iscove NN. . 1996 EMBO J. 15: 7013–7025.

  • Kuramochi S, Moriguchi T, Kuida K, Endo J, Semba K, Nishida E and Karasuyama H. . 1997 J. Biol. Chem. 272: 22679–22684.

  • Kyriakis JM. . 1999 J. Biol. Chem. 274: 5259–5262.

  • Leberer E, Dignard D, Harcus D, Thomas DY and Whiteway M. . 1992 EMBO J. 11: 4815–4824.

  • Lee KK, Murakawa M, Nishida E, Tsubuki S, Kawashima S, Sakamaki K and Yonehara S. . 1998 Oncogene 16: 3029–3037.

  • Lee MH, Reynisdottir I and Massague J. . 1995 Genes Dev. 9: 639–649.

  • Masson D and Kreis TE. . 1993 J. Cell. Biol. 123: 357–371.

  • Nagata S. . 1997 Cell. 88: 355–365.

  • Pombo CM, Bonventre JV, Molnar A, Kyriakis J and Force T. . 1996 EMBO J. 15: 4537–4546.

  • Ramer SW and Davis RW. . 1993 Proc. Natl. Acad. Sci. USA 90: 452–456.

  • Robinson MJ and Cobb MH. . 1997 Curr. Opin. Cell Biol. 9: 180–186.

  • Schinkmann K and Blenis J. . 1997 J. Biol. Chem. 272: 28695–28703.

  • Shi CS and Kehrl JH. . 1997 J. Biol. Chem. 272: 32102–32107.

  • Su YC, Han J, Xu S, Cobb M and Skolnik EY. . 1997 EMBO J. 16: 1279–1290.

  • Taylor LK, Wang HC and Erikson RL. . 1996 Proc. Natl. Acad. Sci. USA 93: 10099–10104.

  • Ushiro H, Tsutsumi T, Suzuki K, Kayahara T and Nakano K. . 1998 Arch. Biochem. Biophys. 355: 233–240.

  • Williamson MP. . 1994 Biochem. J. 297: 249–260.

  • Wilson DJ, Fortner KA, Lynch DH, Mattingly RR, Macara IG, Posada JA and Budd RC. . 1996 Eur. J. Immunol. 26: 989–994.

  • Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME. . 1995 Science 270: 1326–1331.

  • Zhou G, Bao ZQ and Dixon JE. . 1995 J. Biol. Chem. 270: 12665–12669.

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Acknowledgements

We thank Dr Donna Dorow for helpful discussions and for providing the epitope-tagged MAPK and pGEX–c-Jun expression constructs, Dr Steve Gerondakis for providing 12CA5 anti-HA antibodies and Helen Thomas for critical reading of the manuscript. This work was supported by The Angelo and Susan Alberti Program Grant from the Juvenile Diabetes Foundation.

The nucleotide sequences reported in this paper have been submitted to the GenBankTM/EBI Data Bank with accession numbers AF099988, AF099990 and AF099989 for mouse, rat and human SPAK, respectively.

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Authors and Affiliations

  1. Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Parkville, 3050, Australia

    Anne M Johnston, Gaetano Naselli, L Jorge Gonez, Leonard C Harrison & Henry J DeAizpurua

  2. Commonwealth Serum Laboratories, Poplar Road, Parkville, 3050, Australia

    Roland M Martin

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  1. Anne M Johnston
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Johnston, A., Naselli, G., Gonez, L. et al. SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene 19, 4290–4297 (2000). https://doi.org/10.1038/sj.onc.1203784

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