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. 2021 Nov;595(21):2655-2664.
doi: 10.1002/1873-3468.14195. Epub 2021 Oct 10.

3-phosphoinositide-dependent protein kinase 1 (PDK1) mediates crosstalk between Src and Akt pathways in MET receptor signaling

Caroline Molinaro  1 , Alain Martoriati  1 , Arlette Lescuyer  1 , Ingrid Fliniaux  2 , David Tulasne  3 , Katia Cailliau  1
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Free article

3-phosphoinositide-dependent protein kinase 1 (PDK1) mediates crosstalk between Src and Akt pathways in MET receptor signaling

Caroline Molinaro et al. FEBS Lett. 2021 Nov.
Free article

Abstract

The high-affinity tyrosine kinase receptor MET plays a pivotal role in several facets of cell regulation. Although its mitogenic effect is well documented, some aspects of connection patterns between signaling pathways involved in cell cycle progression remain to be deciphered. We have used a tractable heterologous expression system, the Xenopus oocyte, to detect connections between distinct MET signaling cascades involved in G2/M progression. Our results reveal that Src acts as an adapter via its SH2 domain to recruit 3-phosphoinositide-dependent protein kinase 1 (PDK1) to the MET signaling complex leading to Akt phosphorylation. These data define an original crosstalk between Src and Akt signaling pathways that contributes to MET-induced entry into the M phase, and deserves further investigation in pathologies harboring deregulation of this receptor.

Keywords: Akt; G2/M transition; MET signaling; PDK1; Src; Xenopus oocyte; hepatocyte growth factor receptor.

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