PTP1B Is an Effector of Activin Signaling and Regulates Neural Specification of Embryonic Stem Cells
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Cell stem cell |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.sciencedirect.com/science/article/pii/S1934590913004463 |
| Doi | http://dx.doi.org/10.1016/j.stem.2013.09.016 |
| Field | Genetics and molecular biology |
| Keywords | Activin/Nodal; protein tyrosine phosphatase 1B ; Activin/ALK4; p-ERK1/2 ; |
| Description | During embryogenesis, the Activin/Nodal pathway promotes the mesendodermal lineage and inhibits neural fate. The molecular mechanisms underlying this role of the Activin/Nodal pathway are not clear. In this study, we report a role for protein tyrosine phosphatase 1B (PTP1B) in Activin-mediated early fate decisions during ESC differentiation and show that PTP1B acts as an effector of the Activin pathway to specify mesendodermal or neural fate. We found that the Activin/ALK4 pathway directly recruits PTP1B and stimulates its release from the endoplasmic reticulum through ALK4-mediated cleavage. Subsequently, PTP1B suppresses p-ERK1/2 signaling to inhibit neural specification and promote mesendodermal commitment. These findings suggest that a noncanonical Activin signaling pathway functions in lineage specification of mouse and human embryonic stem cells. |
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