Analysis of a Genetic Variant of the Proto-Oncogene Ha-Ras - Identified in a Patient with Premature Aging Syndrome and Insulin Resistance

作者：Knebel B; Haas J; Jacob S; Nitzgen U; Schiller M; Hartwig S; Lehr S; Mueller Wieland D^*; Kotzka J

来源：Diabetologie und Stoffwechsel, 2013, 8(1): 43-50.

DOI：10.1055/s-0032-1330642

• Signaltransduction
• MAPK cascades
• Ha-Ras mutation
• insulin resistance
• growth regulation

Inherited genetic variants of insulin receptor induced cellular signaling have long been suspected to contribute to the development of type-2- diabetes mellitus. In this report we discuss a heterozygous mutation in the first coding exon of the proto-oncogene Ha-Ras (Ha-RasA11P) that we have identified in a patient with familial premature aging syndrome. The patient has atopic sklerodermic skin alterations, insulin resistance as well as disturbances in lipid metabolism. In vitro analyzes have shown that this mutation disrupted not only the signal transduction of the insulin receptor but also other receptor tyrosine kinases, such as IGF-1, EGF, PDGF. These results demonstrate that HA-Ras might have a significant role in insulin sensitivity in humans.

• 出版日期2013-2