Biomedical subjects

Keyong Du

Publications and source records attributed to Keyong Du.

4 recordsLinked to original sources

PubMed2006

TRB3 modulates C2C12 differentiation by interfering with Akt activation.

TRB3 is a member of TRB protein family characterized by containing a variant kinase domain without enzymatic activity. Interacting with Ser/Thr protein kinases Akt, TRB3 impairs Akt activation induced by growth factors and insulin. In this study we have examined the potential role of TRB3 in muscle differentiation. Our data indicated that the expression of TRB3 is downregulated during C2C12 cells undergoing muscle differentiation and that overexpression of TRB3 inhibits Akt activation during differentiation. Correspondingly, overexpression of TRB3 inhibits, while knockdown TRB3 enhances C2C12 differentiation. Thus, our studies indicated that TRB3 plays a critical role in muscle differentiation.

Animals↗

PubMed2005

Regulation of the Akt kinase by interacting proteins.

Ten years ago, it was observed that the Akt kinase is activated by phosphorylation via a phosphoinositide 3-kinase (PI-3K)-dependent process. This discovery generated enormous interest because it provided a link between PI-3K, an enzyme known to play a critical role in cellular physiology, and its downstream targets. Subsequently, it was shown that the activity of the core components of the 'PI-3K/Akt pathway' is modulated by a complex network of regulatory proteins and pathways. Some of the Akt-binding partners modulate its activation by external signals by interacting with different domains of the Akt protein. This review focuses on the Akt interacting proteins and the mechanisms by which they regulate Akt activation.

Oncogene Protein v-akt↗

PubMed2005

Tpl2/cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner.

Macrophages and B-cells from Tpl2 knock-out mice exhibit a restricted defect in lipopolysaccharide and death receptor signaling that is limited to the activation of ERK. Here we show that Tpl2-/- MEFs exhibit defects in ERK, JNK, and NF-kappaB activation, or ERK activation only when stimulated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta, respectively. In addition, we show that the activation of Tpl2 by TNF-alpha depends on signals transduced by both TRAF2 and RIP1. Activated Tpl2 phosphorylates MKK4/SEK1 upstream of JNK and stimulates NF-kappaB DNA binding and transcriptional activity by mechanisms that are independent of the nuclear translocation of p50 and p65. Tpl2-transduced TNF-alpha signals instead promote the phosphorylation of p65 at Ser276 and modulate the spectrum of proteins associated with p65. Phosphorylation stimulates the transcriptional activity of NF-kappaB but does not affect its ability to bind DNA, which may be affected by the composition of the nuclear NF-kappaB complexes. These data confirm that defects caused by a single mutation may be cell-type and signal-specific and delineate the role of Tpl2 in the transduction of TNF-alpha signals that activate JNK and NF-kappaB in MEFs.

Animals↗

PubMed2003

TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver.

Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes.

Adenoviridae↗