title: PTP1B is an effector of activin signaling and regulates neural specification of embryonic stem cells.
abstract: 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.
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Matulka
authors.forename: Hsuan-Hwai
authors.initials: HH
authors.lastname: Lin
authors.forename: Hana
authors.initials: H
authors.lastname: Hříbková
authors.forename: Dafe
authors.initials: D
authors.lastname: Uwanogho
authors.forename: Petr
authors.initials: P
authors.lastname: Dvořák
authors.forename: Yuh-Man
authors.initials: YM
authors.lastname: Sun
mesh_terms: D030201:Activin Receptors, Type I / Q000737:chemistry / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004707:Endoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051899:Smad2 Protein; D028341:Activins; D048049:Extracellular Signal-Regulated MAP Kinases; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I; C498933:Acvr1b protein, mouse; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1