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PMID:18533145

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Citation

Xu, B, Hao, Z, Jha, KN, Zhang, Z, Urekar, C, Digilio, L, Pulido, S, Strauss, JF 3rd, Flickinger, CJ and Herr, JC (2008) Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency. Dev. Biol. 319:211-22

Abstract

Targeted deletion of Tssk1 and 2 resulted in male chimeras which produced sperm/spermatogenic cells bearing the mutant allele, however this allele was never transmitted to offspring, indicating infertility due to haploinsufficiency. Morphological defects in chimeras included failure to form elongated spermatids, apoptosis of spermatocytes and spermatids, and the appearance of numerous round cells in the epididymal lumen. Characterization of TSSK2 and its interactions with the substrate, TSKS, were further investigated in human and mouse. The presence of both kinase and substrate in the testis was confirmed, while persistence of both proteins in spermatozoa was revealed for the first time. In vivo binding interactions between TSSK2 and TSKS were established through co-immunoprecipitation of TSSK2/TSKS complexes from both human sperm and mouse testis extracts. A role for the human TSKS N-terminus in enzyme binding was defined by deletion mapping. TSKS immunoprecipitated from both mouse testis and human sperm extracts was actively phosphorylated. Ser281 was identified as a phosphorylation site in mouse TSKS. These results confirm both TSSK 2 and TSKS persist in sperm, define the critical role of TSKS' N-terminus in enzyme interaction, identify Ser 281 as a TSKS phosphorylation site and indicate an indispensable role for TSSK 1 and 2 in spermiogenesis.

Links

PubMed PMC2670491 Online version:10.1016/j.ydbio.2008.03.047

Keywords

Animals; Genomics; Humans; Infertility, Male/enzymology; Infertility, Male/genetics; Loss of Heterozygosity; Male; Mice; Mice, Knockout; Mice, Mutant Strains; Protein-Serine-Threonine Kinases/deficiency; Protein-Serine-Threonine Kinases/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TSSK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O54887

F

Seeded From UniProt

complete

MOUSE:TSSK2

involved_in

GO:0007286: spermatid development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TSSK2

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TSKS

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O54863

F

Seeded From UniProt

complete

MOUSE:TSSK1

involved_in

GO:0007286: spermatid development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSSK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UJT2

F

Seeded From UniProt

complete

HUMAN:TSSK2

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TSKS

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96PF2

F

Seeded From UniProt

complete


See also

References

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