Selected Reviews

Angiogenesis results in the formation of new blood vessels. Tumor growth, tissue wound and inflammation can induce angiogenesis. Rapid tumor cell growth creates intracellular hypoxia, which initiates a series of cell signaling events that promote angiogenesis. Hypoxia-inducible factor (HIF) is a transcription factor that responds to changing intracellular oxygen concentration. Under typical oxygen levels (normoxia), HIF is hydroxylated and acetylated, modifications that target the transcription factor for VHL mediated ubiquitin degradation. During hypoxia, HIF accumulates and is transported to the nucleus where it induces expression of a wide variety of target gene products, including proteins important for inducing tumor endothelial cell angiogenesis. Growth factors (such as VEGF, FGF, and TGF) induce signaling pathways (including PLCγ, PI3K, Src, Smad signaling) that result in endothelial cell proliferation, increase vascular permeability and cell migration. Extracellular matrix proteases and regulators induce tissue matrix remodeling in preparation for migration of endothelial cells from existing vessels to form new tubing. Cytokines promote additional tumor growth and induce the expression of signaling proteins (i.e. Slit2) that promote the creation of tumor-associated blood vessels. In addition to hypoxia, PI3K and Ras pathways can increase HIF expression by promoting HIF translation. Tissue wounding, ischemia or inflammation recruit macrophage and bone marrow-derived inflammatory cells (BDMC) to wound areas, where these monocytes induce a similar panel of secreted proteins to induce angiogenesis.

Akt Signaling

AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival
Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function
Identification of a proline-rich Akt substrate as a 14-3-3 binding partner
Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils
Control of synaptic strength, a novel function of Akt
Fibronectin protects prostate cancer cells from tumor necrosis factor-alpha-induced apoptosis via the AKT/survivin pathway
Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP)
The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity
Cytoplasmic mislocalization of p27Kip1 protein is associated with constitutive phosphorylation of Akt or protein kinase B and poor prognosis in acute myelogenous leukemia
Hematopoietic cytokines enhance Chk1-dependent G2/M checkpoint activation by etoposide through the Akt/GSK3 pathway to inhibit apoptosis
Lack of PTEN sequesters CHK1 and initiates genetic instability
Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells
From Rapa Nui to rapamycin: targeting PI3K/Akt/mTOR for cancer therapy
Involvement of PI3K/Akt pathway in prostate cancer--potential strategies for developing targeted therapies