Research ArticleNeuroscience

Ligand Binding to LRP1 Transactivates Trk Receptors by a Src Family Kinase–Dependent Pathway

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Science Signaling  28 Apr 2009:
Vol. 2, Issue 68, pp. ra18
DOI: 10.1126/scisignal.2000188

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Transactivated Neurite Outgrowth

The Trk family of receptor tyrosine kinases initiates neurite outgrowth by binding neurotrophic ligands such as nerve growth factor. Shi et al. show that Trk receptor–dependent neurite outgrowth also may occur through an alternative pathway involving the low-density lipoprotein receptor–related protein 1 (LRP1). In PC12 cells and neurons, binding of two structurally distinct ligands to LRP1 activated Src family kinases, which then activated Trk receptors, as measured by Trk receptor tyrosine phosphorylation, the activity of two downstream kinases (Akt and extracellular signal–regulated kinase 1 and 2), and neurite outgrowth assays. In addition, injection of the ligand-binding domain of LRP1 into dorsal root ganglia in rats increased Trk receptor phosphorylation. These results open up the possibility that other LRP1 ligands, such as serpins, lipoproteins, and toxins, also may trigger the transactivation of Trk receptors.

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