title: Serum Inter-α-inhibitor activates the Yes tyrosine kinase and YAP/TEAD transcriptional complex in mouse embryonic stem cells.
abstract: We have previously demonstrated that the Src family kinase Yes, the Yes-associated protein (YAP) and TEA domain TEAD2 transcription factor pathway are activated by leukemia inhibitory factor (LIF) and contribute to mouse embryonic stem (mES) cell maintenance of pluripotency and self-renewal. In addition, we have shown that fetal bovine serum (FBS) induces Yes auto-phosphorylation and activation. In the present study we confirm that serum also activates TEAD-dependent transcription in a time- and dose-dependent manner and we identify Inter-α-inhibitor (IαI) as a component in serum capable of activating the Yes/YAP/TEAD pathway by inducing Yes auto-phosphorylation, YAP nuclear localization and TEAD-dependent transcription. The cleaved heavy chain 2 (HC2) sub-component of IαI, is demonstrated to be responsible for this effect. Moreover, IαI is also shown to efficiently increase expression of TEAD-downstream target genes including well-known stem cell factors Nanog and Oct 3/4. IαI is not produced by the ES cells per se but is added to the cells via the cell culture medium containing serum or serum-derived components such as bovine serum albumin (BSA). In conclusion, we describe a novel function of IαI in activating key pluripotency pathways associated with ES cell maintenance and self-renewal.
authors.affiliation: From the Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75 123 Uppsala, Sweden and.
authors.forename: Sara
authors.initials: S
authors.lastname: Pijuan-Galitó
authors.affiliation: From the Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75 123 Uppsala, Sweden and.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Tamm
authors.affiliation: From the Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75 123 Uppsala, Sweden and GE Healthcare Bio-Sciences AB, SE-751 84 Uppsala, Sweden cecilia.anneren@imbim.uu.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Annerén
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000510:Alpha-Globulins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C101205:TEAD2 protein, human; C486310:Tead2 protein, mouse; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse; C011877:inter-alpha-inhibitor; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; C496639:Yes1 protein, mouse
keywords: Cell Culture; Cell Signaling; Embryonic Stem Cell; Extracellular Matrix; Inter-α-inhibitor; TEAD; Transfection; YAP; Yes