ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation |
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Authors: | Degoutin Joffrey Vigny Marc Gouzi Jean Y |
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Institution: | INSERM, U706/UPMC, Institut du Fer à Moulin, 17 rue du Fer à Moulin, 4 Place Jussieu, F-75005 Paris, France. |
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Abstract: | Activation of the neuronal receptor tyrosine kinase ALK (anaplastic lymphoma kinase) promoted the neuron-like differentiation of PC12 cells through specific activation of the ERK MAP-kinase pathway. However, the nature of primary signaling events initiated is still poorly documented. Here, we established that Shc and FRS2 adaptors were recruited and phosphorylated following antibody-based ALK activation. We further demonstrated that Shc was recruited to the consensus phosphotyrosine site NPTpY(1507) and FRS2 was likely recruited to a novel non-orthodox phosphotyrosine site within ALK. Finally, we characterized a functional role for Shc and likely FRS2 in ALK-dependant MAP-kinase activation and neuronal differentiation of PC12 cells. These findings hence open attractive perspectives concerning specific characteristics of ALK in the control of the mechanisms driving neuronal differentiation. |
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Keywords: | Anaplastic lymphoma kinase Shc FGF receptor substrate 2 Mitogen-activated protein kinase PC12 cells Neurite outgrowth |
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