Increased expression of phosphoinositide 3-kinase (PI3-kinase) mediates elevated tone in the aorta from hypertensive deoxycorticosterone acetate (DOCA)-salt rats. In this article, we hypothesized that (1) alterations observed with respect to PI3-kinase observed in the aorta would also occur in mesenteric resistance arteries responsible for determining total peripheral resistance (TPR) and (2) p...

The key role played by PI3 kinase in cancer, hormone action, and a host of other biological functions suggests that specific inhibitors whose disposition could be ascertained in vivo would be useful in biological research or, potentially, for imaging PI3K in a clinical setting. Wortmannin (Wm, 1) is an inhibitor of PI3 kinase with high specificity for this enzyme. We synthesized three modified ...

Neurite outgrowth is an important process in the formation of neuronal networks. Rac1 and Cdc42, members of the Rho-family GTPases, positively regulate neurite extension through reorganization of the actin cytoskeleton. Here, we examine the dynamic linkage between Rac1/Cdc42 and phosphatidylinositol 3-kinase (PI3-kinase) during nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. ...

3,5,3'-Triiodo-l-thyronine (T(3)), but not l-thyroxine (T(4)), activated Src kinase and, downstream, phosphatidylinositol 3-kinase (PI3-kinase) by means of an alpha(v)beta(3) integrin receptor on human glioblastoma U-87 MG cells. Although both T(3) and T(4) stimulated extracellular signal-regulated kinase (ERK) 1/2, activated ERK1/2 did not contribute to T(3)-induced Src kinase or PI3-kinase ac...

The PI3-K family is one of the most intensely pursued classes of drug targets. This chapter reviews some of the chemical and structural features that determine the selectivity of PI3-K inhibitors, by focusing on a few key compounds that have been instrumental in guiding our understanding of how to design drugs against this family.

OBJECTIVE Ephrin-B2 plays a key role in vascular development. The purpose of this study was to elucidate the molecular mechanisms of ephrin-B2 signaling through the EphB receptor in endothelial cells and to determine whether ephrin-B2 contributes to in vivo angiogenesis in adult mice. METHODS AND RESULTS A chemotaxis assay on a polycarbonate membrane revealed that ephrin-B2/Fc chimeric protei...

Regulation of smooth muscle contraction involves a number of signaling mechanisms that include both kinase and phosphatase reactions. The goal of the present study was to determine the role of one such kinase, phosphatidylinositol (PI)3-kinase, in vascular smooth muscle excitation-contraction coupling. Using intact medial strips of the swine carotid artery, we found that inhibition of PI3-kinas...

It is now known that prenatal ethanol (EtOH) exposure is associated with impaired glucose tolerance and insulin resistance in rat offspring, but the underlying mechanism(s) is not known. To test the hypothesis that in vivo insulin signaling through phosphatidylinositol 3 (PI3)-kinase is reduced in skeletal muscle of adult rat offspring exposed to EtOH in utero, we gave insulin intravenously to ...

BACKGROUND/AIMS Our earlier studies suggested crosstalk between IRS/PI3 kinase/PDK1/Akt/Rac1/ROCK and (Shc2/Grb2/SOS)/Ras/Raf/MEK/ERK pathways downstream PDGF-ββ receptor responsible for chemotaxis and proliferation of malignant mesothelioma cells. The present study was conducted to obtain evidence for this. METHODS To assess activation of Akt, MEK, and ERK, Western blotting was carried out o...

The effect of okadaic acid, a serine/threonine phosphatase inhibitor, was analyzed in two insulin-responsive systems, the isolated mouse soleus muscle and 3T3-L1 adipocytes. While okadaic acid alone was a potent stimulator of glucose transport in both systems, it prevented transport stimulation by insulin. To gain insight into this inhibitory action, the activation of phosphatidylinositol 3-kin...