Figure 8.

IGF-1R as a regulator of access of PTP-1B to GH-activated JAK2. A and B, Diagram highlighting the current findings. A, GH-induced STAT5 activation is enhanced in the presence of IGF-1R. Our findings suggest that IGF-1R, likely by inducibly associating with the GHR-JAK2 complex, prevents access of PTP-1B to its substrate, JAK2, and thereby potentiates GH-induced STAT5 phosphorylation. This blockade of access of PTP-1B may be afforded by IGF-1R itself or by a yet-unidentified IGF-1R-associated protein, here diagrammed as a gray rectangle. B, GH-induced STAT5 activation is diminished in the absence of IGF-1R. When IGF-1R is absent (or dramatically reduced in abundance), it can no longer interact with GHR-JAK2 (or possibly the IGF-1R associated gray rectangle protein); therefore, PTP-1B gains better access to GH-activated JAK2 to dephosphorylate it and diminish acute GH-activated STAT5 signaling.