ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation.

Article Details

Citation

Degoutin J, Vigny M, Gouzi JY

ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation.

FEBS Lett. 2007 Feb 20;581(4):727-34. Epub 2007 Jan 25.

PubMed ID
17274988 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ALK tyrosine kinase receptorQ9UM73Details
Mitogen-activated protein kinase 1P28482Details
Mitogen-activated protein kinase 3P27361Details