Journal
FEBS LETTERS
Volume 581, Issue 4, Pages 727-734Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2007.01.039
Keywords
anaplastic lymphoma kinase; Shc; FGF receptor substrate 2; mitogen-activated protein kinase; PC12 cells; neurite outgrowth
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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 She and FRS2 adaptors were recruited and phosphorylated following antibody-based ALK activation. We further demonstrated that She 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 She 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. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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