Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P19086 (Galphaz)
 110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the ovary it has been demonstrated that PGF(2alpha) activates the phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is known about the downstream signaling events that mediate subsequent cellular responses such as steroidogenesis. The present study was designed to examine the effect of PGF(2alpha) on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization-embryo transfer, were treated with increasing concentrations of PGF(2alpha) (10 nmol/L to 10 micromol/L) for 5 min. For time-course experiments, hGLCs were treated with 1 micromol/L PGF(2alpha) for 1, 5, 10, or 20 min. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (p42(mapk) and p44(mapk), respectively), demonstrated that PGF(2alpha) activated MAPK in hGLCs in a dose- and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC inhibitor), bisindolylmaleimide I (5 micromol/L; a PKC inhibitor), or PD98059 (50 micromol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated the PGF(2alpha)-induced activation of MAPK. In contrast, MAPK activation was not significantly affected by pertussis toxin (200 ng/mL; a G(i) inhibitor) pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were treated with PGF(2alpha) (1 micromol/L), hCG (1 IU/mL), or PGF(2alpha) plus hCG in the presence or absence of PD98059. Progesterone levels in the culture medium were examined by RIA. Treatment of hGLCs with PGF(2alpha) significantly inhibited hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059, reversed the inhibitory effect of PGF(2alpha) on hCG-induced progesterone production. To our knowledge, it is the first demonstration of PGF(2alpha)-induced activation of the MAPK signaling pathway in the human ovary. These results indicated that PGF(2alpha) activated MAPK subsequent to PLC and PKC activation through pertussis toxin-insensitive G protein in hGLCs. Further, we demonstrated that PGF(2alpha)-induced MAPK activation is associated with modulation of progesterone production. These results support the idea that the MAPK signaling pathway is involved in mediating PGF(2alpha) actions in the human ovary.
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PMID:Role of mitogen-activated protein kinase in prostaglandin f(2alpha) action in human granulosa-luteal cells. 1123 27

Macrophages exposed to receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) demonstrate increased DNA synthesis and cell division. In the current study, we have probed the role of cytosolic phospholipase A(2) (cPLA(2)) activity in the cellular response to alpha(2)M*. Ligation of the alpha(2)M* signaling receptor by alpha(2)M*, or its receptor binding fragment, increased cPLA(2) activity 2-3-fold in a concentration and time-dependent manner. This activation required a pertussis toxin-insensitive G protein. Cellular binding of alpha(2)M* also induced transient translocation of cPLA(2) activity to nuclei and membrane fractions. Inhibition of protein kinase C activity or chelation of Ca(2+) inhibited alpha(2)M*-induced increased cPLA(2) activity. Binding of alpha(2)M* to macrophages, moreover, increased phosphorylation of MEK 1/2, ERK 1/2, p38 MAPK, and JNK. Incubation of macrophages with inhibitors of MEK 1/2 or p38 MAPK before stimulation with alpha(2)M* profoundly decreased phosphorylation of MAPKs, blocking cPLA(2) activation. alpha(2)M*-induced increase in [(3)H]thymidine uptake and cell proliferation was completely abolished if activation of cPLA(2) was prevented. The response of macrophages to alpha(2)M* requires transcription factors nuclear factor kappaB, and cAMP-responsive element-binding protein as well as expression of the proto-oncogenes c-fos and c-myc. These studies indicate that the activation of cPLA(2) plays a crucial role in alpha(2)M*-induced mitogenesis and cell proliferation.
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PMID:Regulation of cytosolic phospholipase A2 activity in macrophages stimulated with receptor-recognized forms of alpha 2-macroglobulin: role in mitogenesis and cell proliferation. 1173 96