Shc signaling in differentiating neural progenitor cells.
Previously we found that the availability of ShcA adapter is maximal in neural stem cells but that it is absent in mature neurons. Here we report that ShcC, unlike ShcA, is not present in neural stem/progenitor cells, but is expressed after cessation of their division and becomes selectively enriched in mature neurons. Analyses of its activity in differentiating neural stem/progenitor cells revealed that ShcC positively affects their viability and neuronal maturation via recruitment of the PI3K-Akt-Bad pathway and persistent activation of the MAPK pathway. We suggest that the switch from ShcA to ShcC modifies the responsiveness of neural stem/progenitor cells to extracellular stimuli, generating proliferation (with ShcA) or survival/differentiation (with ShcC).
Conti
L
L
Department of Pharmacological Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
Sipione
S
S
Magrassi
L
L
Bonfanti
L
L
Rigamonti
D
D
Pettirossi
V
V
Peschanski
M
M
Haddad
B
B
Pelicci
P
P
Milanesi
G
G
Pelicci
G
G
Cattaneo
E
E
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005333:Fetus; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D014162:Transfection; D051025:bcl-Associated Death Protein; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D055765:Shc Signaling Adaptor Proteins; D051025:bcl-Associated Death Protein; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases