Angiotensin II-induced insulin resistance and protein tyrosine phosphatases.
Although the importance of protein tyrosine phosphorylation by tyrosine kinases in mitogenic signaling is well-accepted, recent studies also suggest that tyrosine dephosphorylation by protein tyrosine phosphatases (PTPases) play an equally important role. For example, both angiotensin II (Ang II) and insulin are known to mediate protein tyrosine phosphorylation and dephosphorylation events. These apparently paradoxical effects of Ang II and insulin suggest that both convergent and divergent intracellular signaling cascades are stimulated downstream of their respective receptors, producing diverse cellular responses. In this review, we discuss the hypothesis that the protein tyrosine phosphatase (PTPase), PTP-1B, plays a central role in Ang II-induced insulin resistance by inhibiting activation of the insulin receptor. We hypothesize that Ang II-induced PTP-1B activation leads to dephosphorylation of the insulin receptor and that this signaling pathway underlies the maladaptive responses observed in diabetic vascular and renal tissue during type II diabetes.
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Boulevard, Augusta, Georgia 30912-2500, USA. mmarrero@mail.mcg.edu
Mario B
MB
Marrero
David
D
Fulton
David
D
Stepp
David M
DM
Stern
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases