This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spiridonov, N. A. Articles by Johnson, G. R. Search for Related Content PubMed PubMed Citation Articles by Spiridonov, N. A. Articles by Johnson, G. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2005, p. 4250-4261, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4250-4261.2005

Identification and Characterization of SSTK, a Serine/Threonine Protein Kinase Essential for Male Fertility

Nikolay A. Spiridonov,^1* Lily Wong,¹ Patricia M. Zerfas,² Matthew F. Starost,² Svetlana D. Pack,³ Cloud P. Paweletz,^4, and Gibbes R. Johnson^1*

Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892,¹ Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland 20892,² Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,³ Uniformed Services University of the Health Sciences, Department of Anatomy, Physiology and Genetics, Institute of Molecular Medicine, Bethesda, Maryland 20814⁴

Received 26 October 2004/ Returned for modification 22 November 2004/ Accepted 5 February 2005

Here we describe and characterize a small serine/threonine kinase (SSTK) which consists solely of the N- and C-lobes of a protein kinase catalytic domain. SSTK protein is highly conserved among mammals, and no close homologues were found in the genomes of nonmammalian organisms. SSTK specifically interacts with HSP90-1ß, HSC70, and HSP70 proteins, and this association appears to be required for SSTK kinase activity. The SSTK transcript was most abundant in human and mouse testes but was also detected in all human tissues tested. In the mouse testis, SSTK protein was localized to the heads of elongating spermatids. Targeted deletion of the SSTK gene in mice resulted in male sterility due to profound impairment in motility and morphology of spermatozoa. A defect in DNA condensation in SSTK null mutants occurred in elongating spermatids at a step in spermiogenesis coincident with chromatin displacement of histones by transition proteins. SSTK phosphorylated histones H1, H2A, H2AX, and H3 but not H2B or H4 or transition protein 1 in vitro. These results demonstrate that SSTK is required for proper postmeiotic chromatin remodeling and male fertility. Abnormal sperm chromatin condensation is common in sterile men, and our results may provide insight into the molecular mechanisms underlying certain human infertility disorders.

---

* Corresponding author. Mailing address: Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, HFD-122, Bldg. 29A, Rm. 3B-20, 8800 Rockville Pike, Bethesda, Maryland 20892. Phone: (301) 827-1764. Fax: (301) 480-3256. E-mail for Nikolay A. Spiridonov: spiridonov{at}cber.fda.gov. E-mail for Gibbes R. Johnson: johnsong{at}cber.fda.gov.

Present address: Merck and Co., Inc., Molecular Profiling, Rahway, NJ 07065.

---

Molecular and Cellular Biology, May 2005, p. 4250-4261, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.4250-4261.2005

This article has been cited by other articles:

• Sosnik, J., Miranda, P. V., Spiridonov, N. A., Yoon, S.-Y., Fissore, R. A., Johnson, G. R., Visconti, P. E. (2009). Tssk6 is required for Izumo relocalization and gamete fusion in the mouse. J. Cell Sci. 122: 2741-2749 [Abstract] [Full Text]  
• Hahn, K L, Beres, B, Rowton, M. J, Skinner, M K, Chang, Y, Rawls, A, Wilson-Rawls, J (2009). A deficiency of lunatic fringe is associated with cystic dilation of the rete testis. Reproduction 137: 79-93 [Abstract] [Full Text]  
• Su, D., Zhang, W., Yang, Y., Deng, Y., Ma, Y., Song, H., Zhang, S. (2008). Mutation Screening and Association Study of the TSSK4 Gene in Chinese Infertile Men With Impaired Spermatogenesis. J Androl 29: 374-378 [Abstract] [Full Text]  
• Zhang, Z., Shen, X., Jones, B. H, Xu, B., Herr, J. C, Strauss, J. F III (2008). Phosphorylation of Mouse Sperm Axoneme Central Apparatus Protein SPAG16L by a Testis-Specific Kinase, TSSK2. Biol. Reprod. 79: 75-83 [Abstract] [Full Text]