Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways inhibited the growth of TPras transgenic melanomas in severe combined immunodeficient mice, blocked invasive behavior, and reduced angiogenesis. The inhibitor Ly294002, which is specific for phosphatidylinositol 3'-kinase, eff...

Melanoma is a highly aggressive kind of cancer with very poor prognosis. v-Raf murine sarcoma viral oncogene homolog B1 inhibitor vemurafenib has indeed harvested substantial clinical benefits. Nevertheless, its drug resistance also hampered scientists’ efforts towards successful melanoma treatment. In this study, we used data derived from the gene expression omnibus database to analyze effect ...

Norepinephrine and histamine markedly augment accumulations of cyclic AMP elicited by 2-chloroadenosine in a guinea pig cerebral cortical vesicular preparation. In addition, these biogenic amines stimulate phosphatidylinositol turnover. Phosphatidylinositol turnover is associated with mobilization of internal calcium and with stimulation of protein kinase C. Phorbol-12-myristate-13-acetate (PMA...

Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/...

Phosphoinositide kinases play central roles in signal transduction by phosphorylating the inositol ring at specific positions. The structure of one such enzyme, type IIbeta phosphatidylinositol phosphate kinase, reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to one superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 A basic flat...

Adrenomedullin (AM) is a multifunctional peptide in human pheochromocytoma. To evaluate whether AM could be an angiogenic factor, we examined its effect on kinases and angiogenic processes. AM induced tyrosine phosphorylation of Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) by using distinct signaling pathways in human umbilical vein endotheli...

The serine/threonine protein kinase encoded by the Akt proto-oncogene is catalytically inactive in serum-starved primary and immortalized fibroblasts. Here we show that Akt and the Akt-related kinase AKT2 are activated by PDGF. The activation was rapid and specific, and it was abrogated by mutations in the Akt Pleckstrin homology (PH) domain. The Akt activation was also shown to depend on PDGFR...