NCBI Summary:
This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. [provided by RefSeq, Jul 2008]
JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice. Huang K et al. (2017) In female mammals, primordial follicles consist of two types of cells, namely, oocytes and pregranulosa cells that surround the oocytes. The size of the primordial follicle pool determines the reproductive ability of female mammals. However, the underlying mechanisms controlling primordial follicle assembly remain unclear. In this study, we show that oocyte-derived Janus kinase (JAK) signaling is vital for germline cyst breakdown and primordial follicle formation in vitro JAK2 and JAK3 activity is increased while germline cysts are breaking down. Inhibition of either JAK2 or JAK3 prevents germline cyst breakdown and primordial follicle formation. We further show that specific suppression of JAK2 delays germ cell loss through the downregulation of p53, but has no influence on pregranulosa cell proliferation. Alternatively, specific inhibition of JAK3 decreases pregranulosa cell proliferation by downregulating Notch2 signaling, implying that JAK3 acts on pregranulosa cells by controlling the extracellular secretion of oocyte-derived factors. In summary, our results indicate that JAK signaling contributes to germline cyst breakdown and primordial follicle formation by regulating oocyte loss and pregranulosa cell proliferation in the fetal mouse ovary. Our findings contribute to a better understanding of the molecular mechanism of mammalian folliculogenesis.//////////////////
Expression regulated by
LH
Comment
Carvalho CR, et al reported a novel signal transduction pathway for luteinizing hormone and its interaction with insulin and the activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways.
The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study the authors showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry the authors demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.
Ovarian localization
Oocyte, Theca
Comment
Localization of janus kinase 2 to the nuclei of mature oocytes and early cleavage stage mouse embryos.
Ito M, et al 2004 .
Jak2, which is a member of the Janus tyrosine kinase family, plays essential roles in cytokine signal transduction and in the regulation of cell growth and gene expression. To investigate the involvement of Jak2 in the regulation of early preimplantation development, we examined the expression of Jak2 in mouse embryos. Reverse transcription-polymerase chain reaction assays revealed that the relative amount of Jak2 mRNA was highest in unfertilized oocytes, gradually decreased until the four-cell stage, and remained at low levels until the blastocyst stage. Immunocytochemistry showed that Jak2 was localized predominantly to the female pronucleus in one-cell embryos. The immunofluorescence signal was very weak or undetectable in the male pronucleus. In unfertilized oocytes and one-cell embryos at M phase, Jak2 was localized to the chromosomes. After cleavage to the two-cell stage, the intensity of the immunofluorescence signal decreased in the nucleus while the embryos were in late G2. This decrease was independent of DNA synthesis because it was not affected by inhibition of DNA replication. However, inhibition of protein synthesis repressed the disappearance of Jak2 from the nucleus. These results suggest a novel function for Jak2 in the regulation of early preimplantation development.