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

Author:

Spiridonov Nikolay A.1,Wong Lily1,Zerfas Patricia M.2,Starost Matthew F.2,Pack Svetlana D.3,Paweletz Cloud P.4,Johnson Gibbes R.1

Affiliation:

1. Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

2. Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland 20892

3. Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

4. Uniformed Services University of the Health Sciences, Department of Anatomy, Physiology and Genetics, Institute of Molecular Medicine, Bethesda, Maryland 20814

Abstract

ABSTRACT 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 HSP90-1β, 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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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