Figure 8.

Illustrating our working hypothesis for the SHP-1-induced disruption of Ang-1/Tie-2 signaling under HG conditions and in diabetes. (a) In a resting state, SHP-1 maintains Tie-2 inactivation. (b) Stimulation with Ang-1 causes a dissociation of SHP-1 and Tie-2, thus leading to Tie-2 tyrosine phosphorylation, and its downstream signaling Akt and eNOS activation. (c) Stimulation with Ang-1 fails to lead to the dissociation of SHP-1 and Tie-2, thus resulting in a disruption of Ang-1/Tie-2 signaling under hyperglycemic conditions and in diabetes. NG: normal glucose; HG: high glucose; SHP-1: protein tyrosine phosphatase-1.