Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Src homology 2 (SH2) B adaptor protein 1 (SH2B1; originally named SH2-B) is a member of a family of adaptor proteins that influences a variety of signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases. Although SH2B1 performs classical adaptor functions, such as recruitment of specific proteins to activated receptors, it also demonstrates a unique ability to enhance the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2, as well as that of several receptor tyrosine kinases. SH2B1 is also among a small number of adaptor proteins shown to undergo nucleocytoplasmic shuttling, although its exact role within the nucleus is not yet clear. Deletion of the SH2B1 gene results in severe obesity and both leptin and insulin resistance, as well as infertility, which might be a consequence of resistance to insulin-like growth factor I. Thus, knockout mice support a role for SH2B1 as a positive regulator of JAK2 signaling pathways initiated by leptin, as well as of pathways initiated by insulin and, potentially, by insulin-like growth factor I.
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PMID:SH2B1 (SH2-B) and JAK2: a multifunctional adaptor protein and kinase made for each other. 1714 Aug 4

Klinefelter's syndrome is an important genetic cause of infertility in males. Two cases are described, which were picked up at the sexually transmitted infection (STI) clinic because of the finding of unusually small testes. Physicians at STI clinics are uniquely placed to detect this condition as they examine the genitalia of thousands of healthy young men each year as part of a sexual health check up. Benefit of early diagnosis and treatment includes improved quality of life and avoidance of serious complications.
Int J STD AIDS 2007 Jul
PMID:Two cases of Klinefelter's syndrome diagnosed at a sexually transmitted infection clinic. 1762 9

Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.
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PMID:Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1. 1763 Oct 2

We present a 21-year-old woman with a short history of pelvic pain. The history was unremarkable apart from that of undergoing a surgical termination of pregnancy (TOP) some three-and-half years ago. Examination revealed a foreign body at the cervical os. Subsequent investigations revealed more foreign bodies within the cervical canal and uterine cavity, which were removed. Histologically these were found to be bones. Removal of the bone fragment initially discovered lead to an improvement of symptoms. Although the patient was treated for pelvic-inflammatory disease, no infective cause could be established. The condition of intrauterine retained fetal bones is recognized, but rare. Patients experiencing pelvic pain usually present sooner after TOP than did this patient. Although rare, it is an important condition to diagnose as it represents a treatable cause of infertility.
Int J STD AIDS 2008 May
PMID:An unusual case of pelvic pain: retention of fetal bone after abortion. 1848 71

The human endometrium undergoes cyclical changes including proliferation, differentiation, tissue breakdown, and shedding (menstruation) throughout a woman's reproductive life. The postovulatory rise in ovarian progesterone induces profound remodeling and differentiation of the estradiol-primed endometrium. This change, termed decidualization, is crucial for embryo implantation and maintenance of the pregnancy. To date, activation and crosstalk of cAMP- and progesterone-mediated signaling pathways have emerged as key cellular events to drive integrated changes at both the transcriptome and the proteome levels. This results in the induction and maintenance of the decidual phenotype and function. Our recent series of studies highlights the critical role of SRC kinase activation (v-src sarcoma viral oncogene homolog) and STAT5 (signal transducer and activator of transcription 5) phosphorylation in decidualization. After separation of the functional layer of the differentiated endometrium that follows progesterone withdrawal, i.e., menstruation, the basal layer of the endometrium, under the influence of estradiol, regrows and initiates a unique form of angiogenesis and regenerates a new functional layer. The molecular and cellular mechanisms for this process remain elusive, mainly because of difficulties in reproducing menstrual tissue breakdown, shedding, and subsequent tissue regeneration in vitro. We have recently developed a "humanized" mouse model in which a functional human endometrium is reconstituted. It may be used as an in vivo experimental tool for the study of endometrial angiogenesis and regeneration. This model may also be used to identify and test new therapeutic strategies for endometriosis, endometrial cancer, implantation failure, and infertility related to endometrial dysfunction.
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PMID:Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium. 1858 40

Ureaplasma urealyticum is a causative agent of non-gonococcal urethritis and is implicated in the pathogenesis of prostatitis, epididymitis and infertility. The organism is more common in partners of infertile than fertile marriages. U. urealyticum infections not only jeopardize fertility but also pose a risk for infertility treatment and resulting pregnancies. The aim of this study was to determine the prevalence of U. urealyticum and Ureaplasma parvum in semen of infertile and healthy men by polymerase chain reaction (PCR). Semen samples were obtained from infertile patients and healthy controls and were subjected to the routine andrological analysis and PCR. DNA was extracted by the Cadieux method, and analysed by PCR protocol with specific primers for urease and multiple-banded antigen genes. Ureaplasmas were detected significantly by PCR in 12 of 100 (12%) semen specimens from infertile patients and in three of 100 (3%) healthy men. The volume of semen fluid, concentration of sperm cells, and sperm cell with normal morphology were significantly decreased in infertile men. In the group of infertile patients with PCR positive for Ureaplasmas, the volume, count and morphology of semen samples were lower than in the infertile patients with PCR-negative results. U. urealyticum species in semen of infertile men was found to be high (9%) than in healthy controls (1%). Detection rate for U. parvum was 3% in the infertile group and 2% in healthy men. The results indicate that U. urealyticum species is more common in specimens of infertile men. The percentage of normal sperm cells, the volume of semen and the percentage of sperm cells with motility in the PCR positive for U. urealyticum species group were lower than in the PCR positive for U. parvum group.
Int J STD AIDS 2009 Jun
PMID:Prevalence of Ureaplasma urealyticum and Ureaplasma parvum in semen of infertile and healthy men. 1971 Mar 50

Bacterial vaginosis (BV) is a common disorder of the genital tract in women characterized by an alteration of the normal acidic lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by Gardnerella vaginalis, mycoplasma species and anaerobes, with an increase in pH. The present study evaluated whether BV is associated with reproductive complications in women. BV was screened with a Gram stain of vaginal smear and interpretation was done using the Nugent score. Wet mount and polymerase chain reaction were used to screen other infections. Among 510 enrolled women, 72 (14.1%) had BV. Statistical analysis between the BV negative and positive population revealed a significant association (P = 0.0001) with infertility. In pregnant women, the infection rate was low (P = 0.01). Multiple infections such as Candida, Chlamydia and human papilloma virus were observed in 4.2%, 15.3% and 8.3% of BV-infected women, respectively. Results suggest that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment.
Int J STD AIDS 2009 Nov
PMID:Bacterial vaginosis: a cause of infertility? 1983 94

A fully developed, functional epididymis is important for male fertility. In particular, it is apparent that without the most proximal region, the initial segment (IS), infertility results. Therefore, it is important to understand the development and regulation of this crucial epididymal region. We have previously shown that many functions of the IS are regulated by luminal fluid factors/lumicrine factors from the testis. This study provides evidence that lumicrine factors activated the ERK pathway only in epithelial cells of the IS from Postnatal Day (P) 14 to P19 and sustained this activation into adulthood. The activated ERK pathway promoted cell proliferation and differentiation in the developing IS, although in the adult, its role was switched to maintain cell survival. To understand further the regulation of cell proliferation in the IS, we examined the role of DUSP6, an MAPK1/3 (ERK1/2) preferred phosphatase that is also regulated by lumicrine factors in the IS. Utilizing Dusp6(-/-) mice, our studies, surprisingly, revealed that Dusp6 was a major regulator of cell proliferation in the caput and corpus regions, whereas components of the ERK pathway, together with PTEN and SRC, were the major regulators of cell proliferation in the IS. We hypothesize that region-specific regulation of cell proliferation is caused by differences in the balance of activities between pro- and antiproliferation signaling pathway components for each epididymal region. An understanding of the mechanisms of cell proliferation may provide clues as to why the epididymis rarely succumbs to cancer.
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PMID:p-MAPK1/3 and DUSP6 regulate epididymal cell proliferation and survival in a region-specific manner in mice. 2065 Aug 83

Hyperprolactinemia is a major cause of infertility, brought about by inhibition of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus and impairment of luteinizing hormone (LH) output from the pituitary gland. However, whereas the actions of prolactin (PRL) within the brain have been investigated extensively, its specific effects at the level of pituitary gonadotroph target cells remain unclear. Here, we provide evidence that the actions of PRL within the gonadotroph are more complex than originally envisaged. Using a gonadotroph cell monoculture, the first series of experiments showed that PRL is, paradoxically, a potent stimulator of LH release, with a three- to fourfold increase in LH values at hyperprolactinemic concentrations of PRL. Conversely, PRL dose-dependently modulated the LH secretory response to GnRH in a biphasic manner, with classical suppression of LH output only detected under a narrow dose range. In contrast, at all doses tested, PRL blocked the LHB mRNA response to the secretagogue. Subsequent studies revealed that the stimulatory effects of PRL on LH release are not mediated by the conventional cytokine receptor pathways but, rather, by a novel JAK2-PIK3-PKC-dependent signaling cascade. Moreover, the experiments showed that these actions of PRL within gonadotroph cells are controlled by dopamine, the main hypothalamic inhibitory regulator of PRL release in vivo. Our findings have unraveled specific actions of PRL within the gonadotroph and the cell-signaling interactions that ultimately underlie hyperprolactinemia-induced infertility.
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PMID:Characterization of the effects of prolactin in gonadotroph target cells. 2072 Jan 66

Genital infection with Chlamydia trachomatis is common, often asymptomatic, yet capable of causing extensive pelvic damage leading to infertility and tubal ectopic pregnancy. Reducing the impact of chlamydial infection involves developing and applying reliable criteria for screening sexually active adolescents and adults, using accurate screening methods for both women and men, ensuring that patients comply with the very effective treatment regimens, and effecting behavioural change that will diminish the risk of STD transmission.
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PMID:Chlamydia trachomatis: Clinical aspects of preventing tubal infertility and ectopic pregnancies. 2122 52


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