Camk4 is a multifunctional serine/threonine protein kinase with limited tissue distribution that has been implicated in transcriptional regulation in lymphocytes, neurons, and male germ cells. In the mouse testis, however, Camk4 is expressed in spermatids and associated with chromatin and nuclear matrix. Elongating spermatids are not transcriptionally active, raising the possibility that Camk4 has a novel function in male germ cells.
NCBI Summary:
The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells.
General function
Comment
Cellular localization
Cytoplasmic, Nuclear
Comment
Ovarian function
Follicle development, Ovulation
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa, Theca
Comment
Upregulation of Basal Transcriptional Activity of the Cytochrome P450 Cholesterol Side-chain Cleavage (CYP11A) Gene by Isoform-Specific Calcium-Calmodulin-Dependent Protein Kinase in Primary Cultures of Ovarian Granulosa Cells.
Seals RC et al 2004,
Intracellular calcium ions (Ca(2+)) regulate steroidogenesis in the placenta, adrenal gland, testis and ovary. Earlier data indicate that Ca(2+)/calmodulin-dependent protein kinase (CamK) may mediate Ca(2+)-dependent up-regulation of CYP11A (cholesterol side-chain cleavage). To examine this notion further, we assessed the expression and actions of isotype-specific CamK on in vitro transcription of the swine CYP11A gene promoter in primary cultures of ovarian granulosa-luteal cells. RT-PCR and oligodeoxynucleotide sequencing identified gene transcripts encoding CamKII and IV in granulosa and theca cells and corpora lutea. DNA sequence homology with the cognate human and rat genes was 97% and 94% (CamKII) and 96% and 88% (CamKIV), respectively. SDS-PAGE and isoform-specific immunoblotting corroborated expression of CamKII ( approximately 52 kDa) and CamKIV ( approximately 60 kDa) proteins. To monitor transcriptional control, granulosa-luteal cells were transfected transiently with a putative 5'-upstream regulatory region of the homologous CYP11A gene -2320 to +23 bp from the transcriptional start site driving luciferase (CYP11A/luc). Co-expression of constitutively active CamKIV elevated basal transcription by 3.5 +/- 0.2 fold (P < 0.001), whereas inactive mutant CamKIV and native CamKII had no effect. Forskolin, an activator of adenylyl cyclase, stimulated expression of CYP11A/luc by 4.5 +/- 0.9 fold (P < 0.001), and did not enhance transcriptional drive by exogenous CamKIV. Preliminary promoter-deletional analyses showed that a proximal 5'-fragment -100 to +23 bp, but not -50/+23 bp, retained full responsiveness to CamKIV (4.5 +/- 0.4 fold; P < 0.001). Threefold cotransfection of -100/+23 bp CYP11A/luc, active CamKIV and a dominant-negative mutant of the cAMP-responsive element binding protein (KCREB, 10, 100, and 250 ng) inhibited CamKIV-stimulated transcriptional activity by 17, 47 and 48% (pooled SEM+/- 2%) [P < 0.01]. KCREB also repressed forskolin's stimulation of -100/+23 CYP11A/luc by 12, 38 and 52% (P < 0.01). Based on these ensemble outcomes, we postulate that endogenous CamKIV may serve as a Ca(2+)-dependent effector mechanism to maintain basal CYP11A gene expression in ovarian granulosa-luteal cells.
Follicle stages
Antral, Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment:Wu JY, et al 20000 reported that female fertility is reduced in mice lacking Ca2+
calmodulin-dependent protein kinase IV.
Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a serine/threonine protein kinase with limited tissue distribution. CaMKIW is highly expressed in
the testis, where it is found in transcriptionally inactive elongating
spermatids.
In the
absence of CaMKIV, the exchange of sperm nuclear basic proteins in male
spermatids is impaired, resulting in male infertility secondary to defective
spermiogenesis. The involvement of CaMKIV in female fertility has not been
addressed. The authors report that female fertility is markedly reduced in
CaMKIV-deficient mice due to impaired follicular development and ovulation.
CaMKIV is expressed in the ovary, where it is localized in granulosa cells. As granulosa cells
differentiate, CaMKIV levels decrease and the kinase translocates from the
nucleus into the cytoplasm. The results demonstrate a critical role for CaMKIV
in female reproduction and point to a potential function in granulosa cell
differentiation.