The creation of diabetes mellitus relies upon the balance between beta-cell proliferation and death. As mitogen-activated protein kinases (MAPK) may control this balance, the intention of this research had been to examine the events resulting in MAPK activation in beta-cells and the outcomes of these events. Overexpression of the SH2-domain containing adaptor protein Shb led to the assembly and activation of multiunit complex composed of no less than Shb, IRS-1, IRS-2, FAK and PI3K. As a result, the phosphorylation of Akt was enhanced under basal conditions in Shb overexpression cells. It was paralleled by an attenuated activation of the MAP kinases ERK1/2. Thus, Shb-induced alterations in the IRS-1/PI3K/Akt/ERK pathway may clarify the increased proliferation and apoptosis of beta-cells overexpressing Shb. The significance of the MAP kinase p38 in nitric oxide- and cytokine-induced beta-cell death has also been researched…
Contents: Role of MAP Kinases in the Life and Death of Beta-cells
Introduction
Background
Proinflammatory cytokines
Nitric oxide
Apoptosis in diabetes mellitus
Pathways underlying E -cell apoptosis
The role of the JAK/STAT pathway in E-cell apoptosis
IRS-2/PKB signaling in control of E-cell survival
Detailed description of E-cell apoptosis/necrosis pathways
MAP kinase pathways
ERK1/2
JNK1/2
P38 MAPK
Upstream kinases that activate p38
Additional upstream activators
Downregulation of the p38 signaling pathway
Downstream substrates of p38 group MAP kinases
Transcription factors activated by p38
Genes regulated by the p38 pathway
P38 and inflammation
P38 and apoptosis
Akt/PKB survival pathway
The role of adapter proteins in signal transduction
The SHB adapter protein
TAB1 adapter protein…
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