Abstract
Protein tyrosine kinases and protein phosphatases play a critical role in cellular regulation. The length of a cellular response depends on the interplay between activating protein kinases and deactivating protein phosphatases. Protein tyrosine phosphatase 1B (PTP1B) and growth factor receptor-bound protein 14 (Grb14) are negative regulators of receptor tyrosine kinases. However, in the retina, we have previously shown that PTP1B inactivates insulin receptor signaling, whereas phosphorylated Grb14 inhibits PTP1B activity. In silico docking of phosphorylated Grb14 and PTP1B indicate critical residues in PTP1B that may mediate the interaction. Phosphoinositides (PIPs) are acidic lipids and minor constituents in the cell that play an important role in cellular processes. Their levels are regulated by growth factor signaling. Using phosphoinositide binding protein probes, we observed increased levels of PI(3)P, PI(4)P, PI(3,4)P2, PI(4,5)P2, and PI(3,4,5)P3 in PTP1B knockout mouse retina and decreased levels of these PIPs in Grb14 knockout mouse retina. These observations suggest that the interplay between PTP1B and Grb14 can regulate PIP metabolism.
Highlights
Protein tyrosine phosphatase 1B (PTP1B) and growth factor receptor-bound protein (Grb14) are two negative regulators of insulin receptor (IR) and insulin-like growth factor1 receptor (IGF-1R) [1,2]
We previously reported that PTP1B and growth factor receptor-bound protein 14 (Grb14) are expressed in various layers of the retina, including photoreceptor cells, where IR and insulin-like growth factor1 receptor (IGF-1R) are expressed [3]
PTP1B and Grb14? We previously reported that Grb14 undergoes tyrosine phosphorylation by a non-receptor tyrosine kinase, Src, and the phosphorylated Grb14 competitively inhibits
Summary
Protein tyrosine phosphatase 1B (PTP1B) and growth factor receptor-bound protein (Grb14) are two negative regulators of insulin receptor (IR) and insulin-like growth factor1 receptor (IGF-1R) [1,2]. Protein tyrosine phosphatase 1B (PTP1B) and growth factor receptor-bound protein (Grb14) are two negative regulators of insulin receptor (IR) and insulin-like growth factor. We previously reported that PTP1B and Grb are expressed in various layers of the retina, including photoreceptor cells, where IR and IGF-1R are expressed [3]. We noted increased PTP1B activity in the dark-adapted retina, and decreased PTP1B activity was observed in the light-adapted conditions [4]. PTP1B belongs to the protein tyrosine phosphatase family, dephosphorylates insulin and IGF1 receptors, and inactivates IR and IGF1R signaling [1]. Either conditional deletion of PTP1B in rods or global PTP1B deletion resulted in enhanced retinal neuroprotection [4,5], whereas mouse rods lacking insulin receptors are susceptible to light-induced photoreceptor degeneration [6]. Deletion of IR resulted in cone degeneration in the absence of stress [7]
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