Masahiro Aoki

The serine-threonine kinase Akt is a downstream target of phosphoinositide 3-kinase (PI 3-kinase); it is activated by the phosphoinositide 3-phosphate-dependent kinases PDK1 and PDK2. Certain mutated forms of Akt induce oncogenic transformation in chicken embryo fibroblast cultures and hemangiosarcomas in young chickens. This ability to transform cells depends on localization of Akt at the plasma membrane and on the kinase activity of Akt. A transdominant negative form of Akt interferes with onc

The oncoproteins P3k (homolog of the catalytic subunit of class IA phosphoinositide 3-kinase) and Akt (protein kinase B) induce oncogenic transformation of chicken embryo fibroblasts. The transformed cells show constitutive phosphorylation of the positive regulator of translation p70S6 kinase (S6K) and of the eukaryotic initiation factor 4E-BP1 binding protein (4E-BP1), a negative regulator of translation. Phosphorylation activates S6K and inactivates 4E-BP1. A mutant of Akt that retains kinase

The P3k oncoprotein [homolog of the catalytic subunit p110alpha of class 1A phosphoinositide 3-kinase (PI3K)] and its downstream effector Akt induce oncogenic transformation in cultures of chicken embryo fibroblasts (CEF). The winged helix transcription factor FoxO1 is a growth-attenuating and proapoptotic protein and serves as a substrate of Akt. Here we show that FoxO1 expression is constitutively suppressed in CEF transformed by P3k or Akt. The FoxO1 protein level is high in serum-starved nor

The interaction between beta-catenin and LEF-1/TCF transcription factors plays a pivotal role in the Wnt-1 signaling pathway. The level of beta-catenin is regulated by partner proteins, including glycogen synthase kinase-3beta (GSK-3beta) and the adenomatous polyposis coli (APC) tumor suppressor protein. Genetic defects in APC are responsible for a heritable predisposition to colon cancer. APC protein and GSK-3beta bind beta-catenin, retain it in the cytoplasm, and facilitate the proteolytic deg

The retroviral oncogene p3k (v-p3k) of avian sarcoma virus 16 (ASV16) codes for the catalytic subunit of phosphoinositide (PI) 3-kinase, p110alpha. The v-P3k protein is oncogenic in vivo and in vitro; its cellular counterpart, c-P3k, lacks oncogenicity. Fusion of viral Gag sequences to the amino terminus of c-P3k activates the transforming potential. Activation can also be achieved by the addition of a myristylation signal to the amino terminus or of a farnesylation signal to the carboxyl termin

HNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of <i>CD44</i> during EMT.

The oncoproteins P3k (homolog of the catalytic subunit of class IA phosphoinositide 3-kinase) and Akt (protein kinase B) induce oncogenic transformation of chicken embryo fibroblasts.The transformed cells show constitutive phosphorylation of the positive regulator of translation p70S6 kinase (S6K) and of the eukaryotic initiation factor 4E-BP1 binding protein (4E-BP1), a negative regulator of translation.Phosphorylation activates S6K and inactivates 4E-BP1.A mutant of Akt that retains kinase act

The cot gene is an oncogene encoding serine/threonine kinases isolated by DNA transfection assay. In this study, we isolated cDNA for the human cot protooncogene (proto-cot gene) and examined the structure and function of its gene products. The proto-cot gene has an open reading frame encoding 467 amino acids of which the first 397 amino acids are identical to those in the corresponding part of the cot gene. The protein products of the proto-cot gene were identified as 58- and 52-kDa proteins wi

This study identifies signaling pathways essential for maintaining the stemness and metastatic potential of colorectal cancer cells and proposes CREB as a therapeutic target in metastatic colorectal cancer.

The products of the cot gene, a novel oncogene isolated by DNA transfection assay using the hamster cell line SHOK, were identified as 46 kDa and 52 kDa proteins by using anti-peptide antibodies. The 46 kDa and 52 kDa proteins both showed autophosphorylation activity at serine residues. The two forms of the Cot protein were suggested to differ in their amino-terminal structures as a result of alternative initiation of translation. Subcellular fractionation revealed that the 46 kDa and 52 kDa pro

Iodothyronine deiodinase 2 (DIO2) converts the prohormone thyroxine (T4) to bioactive T3 in peripheral tissues and thereby regulates local thyroid hormone (TH) levels. Although epidemiologic studies suggest the contribution of TH to the progression of colorectal cancer (CRC), the role of DIO2 in CRC remains elusive. Here we show that Dio2 is highly expressed in intestinal polyps of Apc^Δ716 mice, a mouse model of familial adenomatous polyposis and early stage sporadic CRC. Laser captur