The phosphatase SHP-2 plays an essential role in growth factor signaling and mutations in its locus is the cause of congenital and acquired pathologies. Mutations of SHP-2 are known to affect the activation of the RAS pathway. Gain-of-function mutations cause the Noonan syndrome, the most common non-chromosomal congenital disorder. In order to obtain a holistic picture of the intricate regulatory mechanisms underlying SHP-2 physiology and pathology, we set out to characterize perturbations of the cell phosphorylation profile caused by an altered localization of SHP-2. To describe the proteins whose activity may be directly or indirectly modulated by SHP-2 activity, we identified tyrosine peptides that are differentially phosphorylated in wild type SHP-2 cells and isogenic cells expressing a non-functional SHP-2 variant that cannot dephosphorylate the physiological substrates due to a defect in cellular localization upon growth factor stimulation. By an iTRAQ based strategy coupled to mass spectrometry, we have identified 63 phosphorylated tyrosine residues in 53 different proteins whose phosphorylation is affected by SHP-2 activity. Some of these confirm already established regulatory mechanisms while many others suggest new possible signaling routes that may contribute to the modulation of the ERK and p38 pathways by SHP-2. Interestingly many new proteins that we found to be regulated by SHP-2 activity are implicated in the formation and regulation of focal adhesions.
|Tipologia:||Articolo su rivista|
|Citazione:||Corallino, S., Iwai, L.k., Payne, L.s., Huang, P.h., Sacco, F., Cesareni, G., et al. (2015). Alterations in the phosphoproteomic profile of cells expressing a non-functional form of the SHP2 phosphatase. NEW BIOTECHNOLOGY.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||10.1016/j.nbt.2015.08.002|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2015|
|Titolo:||Alterations in the phosphoproteomic profile of cells expressing a non-functional form of the SHP2 phosphatase|
|Autori interni:||CORALLINO, SALVATORE |
|Autori:||Corallino, S; Iwai, Lk; Payne, Ls; Huang, Ph; Sacco, F; Cesareni, G; Castagnoli, L|
|Appare nelle tipologie:||01 - Articolo su rivista|
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