Gene interactions and pathways from curated databases and text-mining
Mol Biol Cell 2001, PMID: 11452011

Src family kinases are required for prolactin induction of cell proliferation.

Fresno Vara , J A; Cáceres, M A; Silva, A; Martín-Pérez, J

Prolactin (PRL) is a pleiotropic cytokine promoting cellular proliferation and differentiation. Because PRL activates the Src family of tyrosine kinases (SFK), we have studied the role of these kinases in PRL cell proliferation signaling. PRL induced [(3)H]thymidine incorporation upon transient transfection of BaF-3 cells with the PRL receptor. This effect was inhibited by cotransfection with the dominant negative mutant of c-Src (K>A295/Y>F527, SrcDM). The role of SFK in PRL-induced proliferation was confirmed in the BaF-3 PRL receptor-stable transfectant, W53 cells, where PRL induced Fyn and Lyn activation. The SFK-selective inhibitors PP1/PP2 and herbimycin A blocked PRL-dependent cell proliferation by arresting the W53 cells in G1, with no evident apoptosis. In parallel, PP1/PP2 inhibited PRL induction of cell growth-related genes c-fos, c-jun, c-myc, and odc. These inhibitors have no effect on PRL-mediated activation of Ras/Mapk and Jak/Start pathways. In contrast, they inhibited the PRL-dependent stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine phosphatase Shp2, and the PI3K-dependent Akt and p70S6k serine kinases. Consistently, transient expression of SrcDM in W53 cells also blocked PRL activation of Akt. These results demonstrate that activation of SFKs is required for cell proliferation induced by PRL.

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Text Mining Data

Src family of tyrosine kinases (SFK) → PRL: " Because PRL activates the Src family of tyrosine kinases (SFK) , we have studied the role of these kinases in PRL cell proliferation signaling "

Fyn → PRL: " The role of SFK in PRL induced proliferation was confirmed in the BaF-3 PRL receptor-stable transfectant, W53 cells, where PRL induced Fyn and Lyn activation "

Lyn → PRL: " The role of SFK in PRL induced proliferation was confirmed in the BaF-3 PRL receptor-stable transfectant, W53 cells, where PRL induced Fyn and Lyn activation "

PRL ⊣ PP1/PP2: " In parallel, PP1/PP2 inhibited PRL induction of cell growth related genes c-fos, c-jun, c-myc, and odc "

PRL ⊣ PP1/PP2: " In parallel, PP1/PP2 inhibited PRL induction of cell growth related genes c-fos, c-jun, c-myc, and odc "

Sam68 → PRL: " In contrast, they inhibited the PRL dependent stimulation of the SFKs substrate Sam68 , the phosphorylation of the tyrosine phosphatase Shp2, and the PI3K dependent Akt and p70S6k serine kinases "

Akt → PI3K: " In contrast, they inhibited the PRL dependent stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine phosphatase Shp2, and the PI3K dependent Akt and p70S6k serine kinases "

p70S6k → PI3K: " In contrast, they inhibited the PRL dependent stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine phosphatase Shp2, and the PI3K dependent Akt and p70S6k serine kinases "

Shp2 → PRL: " In contrast, they inhibited the PRL dependent stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine phosphatase Shp2 , and the PI3K dependent Akt and p70S6k serine kinases "

PRL → Akt: " Consistently, transient expression of SrcDM in W53 cells also blocked PRL activation of Akt "

Manually curated Databases

No curated data.