Expression and Phosphorylation of Mitogen-Activated Protein Kinases During Spermatogenesis and Epididymal Sperm Maturation in Mice

Lü, Qing; Sun, Qing‐Yuan; Breitbart, Haim; Chen, D Y

doi:10.1080/014850199262733

Cited by 47 publications

(25 citation statements)

References 27 publications

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“…For much of spermiogenesis, spermatids are transcriptionally inactive as a consequence of nuclear condensation, yet pebp proteins persist and are incorporated into spermatozoa along with B-raf, MEK1, and ERK [49,50]. Based on the structural homology with other pebp proteins, several possibilities must be considered for the potential functional roles of the pebps.…”

Section: Discussionmentioning

confidence: 99%

“…Third, the pebps may be regulators of MAP kinase-mediated phosphorylation but not transcriptional activation of proteins involved in posttesticular sperm function, i.e., the MAP kinase pathway may regulate sperm function in a genome independent manner. Several investigators have described the distribution of components of the MAP kinase pathway within the testis and specifically within the haploid germ cell compartment [42,43,49,50]. The precise localization of these components and their significance in a physiological context remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Testis-Specific Member of the Phosphatidylethanolamine Binding Protein Family, pebp-21

Hickox¹,

Gibbs²,

Morrison³

et al. 2002

Biology of Reproduction

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The phosphatidylethanolamine binding proteins (pebps) are an evolutionarily conserved family of proteins recently implicated in mitogen-activated protein (MAP) kinase pathway regulation, where they are called raf kinase inhibitory proteins. Here, we describe the cloning, cellular localization, and partial characterization of a new member, pebp-2, with potential roles in male fertility. Expression data show that pebp-2 is a testis-specific 21-kDa protein found within late meiotic and haploid germ cells in a stage-specific pattern that is temporally distinct from that of pebp-1. Sequence analyses suggest that pebp-2 forms a distinct subset of the pebp family within mammals. Database analyses revealed the existence of a third subset. Analysis suggests that the specificity/regulation of the distinct pebps subsets is likely to be determined by the amino terminal 40 amino acids or the 3' untranslated region, where the majority of sequence differences occur. Protein homology modeling suggests that pebp-2 protein is, however, topologically similar to other pebps and composed of Greek key fold motifs, a dominant beta-sheet formed from five anti-parallel beta strands forming a shallow groove associated with a putative phosphatidylethanolamine binding site. The pebp-2 gene is intronless and data suggest that it is a retrogene derived from pebp-1. Further, pebp-2 colocalizes with members of the MAP kinase pathway in late spermatocytes and spermatids and on the midpiece of epididymal sperm. These data raise the possibility that pebp-2 is a novel participant in the MAP kinase signaling pathway, with a role in spermatogenesis or posttesticular sperm maturation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Testis-Specific Member of the Phosphatidylethanolamine Binding Protein Family, pebp-21

Hickox¹,

Gibbs²,

Morrison³

et al. 2002

Biology of Reproduction

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“…In the present study, we evaluated the importance of HST-1/FGF-4 expression using antisense ODNs in both in vitro and in vivo studies. Since constitutive activation of the tyrosine-kinase receptor has been linked to drug resistance and anti-apoptotic and accelerated tumor cell growth [27], further analysis is required to learn whether inhibition of ligand expression leads to protein kinase inactivation, which results in the suppression of a germ cell tumor. In conclusion, our data represent that antisense HST-1/FGF-4 ODNs mixed with Atelocollagen inhibit the growth and the metastatic behavior of NEC8 cells, indicating a novel therapeutic approach for human testicular tumors.…”

Section: Discussionmentioning

confidence: 99%

Antisense oligodeoxynucleotide against HST‐1/FGF‐4 suppresses tumorigenicity of an orthotopic model for human germ cell tumor in nude mice

Hirai

Sasaki

Sanada³

et al. 2003

The Journal of Gene Medicine

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“…The two forms of MAPK, ERK1 and ERK2, are expressed in similar quantities in all spermatogenic cells at different stages (2). However, evidence of ERK1/2 phosphorylation has been detected only in early spermatogenic cells from primitive spermatogonia to zygotene spermatocytes (30). Indeed, ERK translocates to the nucleus and activates several transcription factors, like c-Fos, c-Jun, Elk-1, Ets, STAT, and CREB, culminating in proliferation and differentiation.…”

mentioning

confidence: 99%

“…FGF binds to and activates a family of receptor tyrosine kinases. This leads to the activation of multiple signal transduction pathways, for instance, the MAPKs ERK1 and ERK2, which are present and active in sperm cells (2,3,28,30,31). The two forms of MAPK, ERK1 and ERK2, are expressed in similar quantities in all spermatogenic cells at different stages (2).…”

mentioning

confidence: 99%

Sertoli-secreted FGF-2 induces PFKFB4 isozyme expression in mouse spermatogenic cells by activation of the MEK/ERK/CREB pathway

Gómez

Manzano

Figueras

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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In this study, we investigated how the hormonal regulation of spermatogenesis modulates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) isozyme expression in two mouse spermatogenic cell lines, GC-1 spg and GC-2 spd (ts). For this purpose, TM4 Sertoli cells were used to obtain conditioned medium that was treated or not with dihydrotestosterone for 2 days [dihydrotestosterone conditioned medium (TCM) and basal conditioned medium (BCM), respectively]. We observed an increase in the expression of PFKFB4 along with a decrease in PFKFB3 in spermatogenic cell lines treated with TCM. These effects were inhibited by the antiandrogen drug flutamide and by heat-inactivated TCM, indicating the protein nature of the TCM mediator and its dependence on Sertoli cell stimulation by dihydrotestosterone. In addition, adult rat testes treated with the GnRH antagonist Degarelix exhibited a reduction in the expression of PFKFB4 in germ cells. Addition of exogenous FGF-2 mimicked the changes in the Pfkfb gene expression, whereas neutralizing antibodies against FGF-2 abolished them. Interestingly, similar effects on Pfkfb gene expression were observed using different MAPK inhibitors (U-0126, PD-98059, and H-89). Luciferase analysis of Pfkfb4 promoter constructs demonstrated that a putative CRE-binding sequence located at Ϫ1,463 relative to the transcription start site is required to control Pfkfb4 gene expression after TCM treatment. Pulldown assays showed the binding of the CREB transcription factor to this site. Altogether, these results show how the paracrine regulation orchestrated by Sertoli cells in response to testosterone controls glycolysis in germ cells.fibroblast growth factor; 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase; mitogen-activated protein kinase kinase; extracellular signal-regulated kinase; cAMP response element-binding protein; fructose-2,6-bisphosphate; glycolysis; spermatogenesis; sperm production

show abstract

Expression and Phosphorylation of Mitogen-Activated Protein Kinases During Spermatogenesis and Epididymal Sperm Maturation in Mice

Cited by 47 publications

References 27 publications

Identification of a Novel Testis-Specific Member of the Phosphatidylethanolamine Binding Protein Family, pebp-21

Identification of a Novel Testis-Specific Member of the Phosphatidylethanolamine Binding Protein Family, pebp-21

Antisense oligodeoxynucleotide against HST‐1/FGF‐4 suppresses tumorigenicity of an orthotopic model for human germ cell tumor in nude mice

Sertoli-secreted FGF-2 induces PFKFB4 isozyme expression in mouse spermatogenic cells by activation of the MEK/ERK/CREB pathway

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