Cloning and Chromosomal Localization of a Gene Encoding a Novel Serine/Threonine Kinase Belonging to the Subfamily of Testis-Specific Kinases

Visconti, Pablo E.; Hao, Zhonglin; Purdon, Marie A.; Stein, Paula; Balsara, Binaifer; Testa, Joseph R.; Herr, John C.; Moss, Stuart B.; Kopf, Gregory S.

doi:10.1006/geno.2001.6628

Cited by 35 publications

(32 citation statements)

References 25 publications

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“…Targeted deletion of the casein kinase 2␣Ј catalytic subunit leads to oligozoospermia and extensive degeneration of germ cells at all stages of spermatogenesis (5), and Cdk2 is essential for completing mitotic division in germ cells (6). Three members of the testis-specific serine threonine kinase (TSSK) 2 family, namely TSSK1, TSSK2, and the small serine/threonine kinase (SSTK, also known as TSSK6), are expressed postmeiotically and are essential for male fertility (7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase

Jha

Wong

Zerfas

et al. 2010

Journal of Biological Chemistry

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We previously reported the identification of small serine/ threonine kinase (SSTK) that is expressed in postmeiotic germ cells, associates with HSP90, and is indispensable for male fertility. Sperm from SSTK-null mice cannot fertilize eggs in vitro and are incapable of fusing with eggs that lack zona pellucida. Here, using the yeast two-hybrid screen, we have discovered a novel SSTK-interacting protein (SIP) that is expressed exclusively in testis. The gene encoding SIP is restricted to mammals and encodes a 125-amino acid polypeptide with a predicted tetratricopeptide repeat domain. SIP is co-localized with SSTK in the cytoplasm of spermatids as they undergo restructuring and chromatin condensation, but unlike SSTK, is not retained in the mature sperm. SIP binds to SSTK with high affinity (K d ϳ10 nM), and the proteins associate with each other when co-expressed in cells. In vitro, SIP inhibited SSTK kinase activity, whereas the presence of SIP in cells resulted in enzymatic activation of SSTK without affecting Akt or MAPK activity. SIP was found to be associated with cellular HSP70, and analyses with purified proteins revealed that SIP directly bound HSP70. Importantly, SSTK recruited SIP onto HSP90, and treatment of cells with the specific HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, completely abolished SSTK catalytic activity. Hence, these findings demonstrate that HSP90 is essential for functional maturation of the kinase and identify SIP as a cochaperone that is critical to the HSP90-mediated activation of SSTK.Protein phosphorylation plays important roles during spermatogenesis (1, 2). A number of protein kinases are expressed in testis, and several of them are essential for male fertility (3). For example, disruption of the Camk4 which is involved in postmeiotic chromatin condensation, results in impaired spermiogenesis and male sterility (4). Targeted deletion of the casein kinase 2␣Ј catalytic subunit leads to oligozoospermia and extensive degeneration of germ cells at all stages of spermatogenesis (5), and Cdk2 is essential for completing mitotic division in germ cells (6). Three members of the testis-specific serine threonine kinase (TSSK) 2 family, namely TSSK1, TSSK2, and the small serine/threonine kinase (SSTK, also known as TSSK6), are expressed postmeiotically and are essential for male fertility (7-13).SSTK is one of the smallest protein kinases, consists only of N-and C-lobes of a kinase catalytic domain, and forms stable associations with heat shock protein (HSP) 70 and 90 (7). Targeted deletion of Sstk in mice resulted in male infertility without any other visible somatic defects. SSTK-null sperm could not fertilize eggs in vitro and are incapable of fusing with eggs that lack zona pellucida (9). SSTK expression first appears in elongating spermatids as they undergo cellular remodeling and chromatin condensation, and the kinase is retained in mature sperm. However, the in vivo substrate(s) for SSTK, the mechanism of activation, and the specific function that SSTK performs in spe...

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confidence: 99%

Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase

Jha

Wong

Zerfas

et al. 2010

Journal of Biological Chemistry

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“…Therefore, proteins that are synthesized during spermatogenesis and spermiogenesis are necessary for spermatid differentiation and/or for sperm function during fertilization. It has been reported that some proteins are specifically expressed during the spermatogenic process and then located in spermatozoa (Visconti et al 2001;Li et al 2002;Hao et al 2004;Li et al 2006). In the case of TDRG1, although its specific expression in testis has been identified (Jiang et al 2011), the distribution profile and possible function of TDRG1 in human spermatozoa remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Expression and Localization of Testis Developmental Related Gene 1 (TDRG1) in Human Spermatozoa

Chen

Sun

et al. 2015

Tohoku J. Exp. Med.

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Testis-specific proteins, synthesized during spermatogenesis and spermiogenesis, are necessary for spermatid differentiation and/or for mature sperm function during fertilization. However, majority of these genes have neither been identified nor fully characterized. Testis developmental related gene 1 (TDRG1), a newly identified human testis-specific gene, encodes a 100-amino-acid protein without any characterized protein domains, and it may play a role in spermatogenesis. However, whether this human-specific protein is important for mature sperm function remains unclear. As an initial effort, in this study, we aimed to systematically investigate the expression and localization of TDRG1 in normal human spermatozoa. Thus, immunohistochemistry was used to analyze the distribution of TDRG1 in human testis. Reverse transcription-polymerase chain reaction, western blot analysis and indirect immunofluorescence were used to determine the expression and localization of TDRG1 in normal human spermatozoa. The immunohistochemistry results showed that the TDRG1 protein was expressed in spermatogenic cells in the seminiferous tubules of human testis. Interestingly, the TDRG1 was more abundant in spermatogenic cells at the late stages of spermatogenesis. The TDRG1 antibody specifically recognized an 11-kDa protein only in soluble extracts from normal human spermatozoa. Indirect immunofluorescence assays indicated that TDRG1 located in the midpiece, principal piece and flagellum of normal human spermatozoa. In conclusion, TDRG1 was found not only in spermatogonia, but also in spermatozoa. The localization of TDRG1 in human normal spermatozoa implies its potential regulatory role in sperm motility.

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“…The expression of TSSK1 and TSSK2 is limited to meiotic and postmeiotic spermatogenic cells, respectively [7,12]. TSSK3 presents exclusively in and may function in Leydig cells [8,13]. TSSK4 phosphorylates the cAMP responsive element binding protein, which is important for germ cell differentiation [10,14].…”

Section: Introductionmentioning

confidence: 99%

c.822+126T>G/C: a novel triallelic polymorphism of the TSSK6 gene associated with spermatogenic impairment in a Chinese population

Su¹,

Zhang²,

Yang³

et al. 2009

Asian J Androl

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Cloning and Chromosomal Localization of a Gene Encoding a Novel Serine/Threonine Kinase Belonging to the Subfamily of Testis-Specific Kinases

Cited by 35 publications

References 25 publications

Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase

Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase

Expression and Localization of Testis Developmental Related Gene 1 (TDRG1) in Human Spermatozoa

c.822+126T>G/C: a novel triallelic polymorphism of the TSSK6 gene associated with spermatogenic impairment in a Chinese population

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