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Originally published In Press as doi:10.1074/jbc.M208601200 on February 6, 2003

J. Biol. Chem., Vol. 278, Issue 15, 13520-13530, April 11, 2003
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Identification and Characterization of a Novel Ste20/Germinal Center Kinase-related Kinase, Polyploidy-associated Protein Kinase*

Kazuo NishigakiDagger §, Delores ThompsonDagger , Takashi YugawaDagger , Karen RulliDagger , Charlotte HansonDagger , Joan CmarikDagger , J. Silvio Gutkind, Hidemi Teramoto, and Sandra RuscettiDagger ||

From the Dagger  Basic Research Laboratory, NCI, National Institutes of Health, Frederick, Maryland and  Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892

A novel protein kinase, polyploidy-associated protein kinase (PAPK), was isolated using a subtraction cDNA library approach from a mouse erythroleukemia cell line that had been induced to polyploidy after serum withdrawal. PAPK shares homology with members of the Ste20/germinal center kinase family of protein kinases and is ubiquitously expressed as two spliced forms, PAPK-A and PAPK-B, that encode for proteins of 418 and 189 amino acids, respectively. The expression of endogenous PAPK-A protein increased after growth factor withdrawal in murine hematopoietic and fibroblast cells. When tested in an in vitro kinase assay, PAPK-A was activated in response to the stress-inducing agent hydrogen peroxide and slightly by fetal calf serum. Biochemical characterization of the PAPK-A-initiated pathway revealed that this novel kinase does not affect MAP kinase activity but can stimulate both c-Jun N-terminal kinase 1 (JNK1) and ERK6/p38gamma . The kinase activity of PAPK appears to be required for the activation of ERK6/p38gamma but not JNK1. When an inducible construct of PAPK-A was expressed in stably transfected NIH3T3 cells, the cells exhibited distinct cytoskeletal changes and became resistant to apoptotic cell death induced by serum withdrawal, effects of PAPK that require its kinase activity. These data suggest that PAPK is a new member of the Ste20/germinal center kinase family that modulates cytoskeletal organization and cell survival.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence may be addressed: Basic Research Laboratory, Bldg. 469, Rm. 205, NCI-Frederick, Frederick, MD 21702-1201. Tel.: 301-846-5740; Fax: 301-846-6164; E-mail: nishigakik@mail.ncifcrf.gov.

|| To whom correspondence may be addressed: Basic Research Laboratory, Bldg. 469, Rm. 205, NCI-Frederick, Frederick, MD 21702-1201. Tel.: 301-846-5740; Fax: 301-846-6164; E-mail: ruscetti@ncifcrf.gov.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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