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3‐phosphoinositide‐dependent protein kinase 1 (PDK1) mediates crosstalk between Src and Akt pathways in MET receptor signaling
Author(s) -
Molinaro Caroline,
Martoriati Alain,
Lescuyer Arlette,
Fliniaux Ingrid,
Tulasne David,
Cailliau Katia
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14195
Subject(s) - proto oncogene tyrosine protein kinase src , microbiology and biotechnology , protein kinase b , crosstalk , phosphoinositide 3 kinase , signal transduction , biology , phosphorylation , receptor tyrosine kinase , pi3k/akt/mtor pathway , cancer research , physics , optics
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.