Protein Kinase A Activation of the Surfactant Protein B Gene Is Mediated by Phosphorylation of Thyroid Transcription Factor 1

Yan, Cong; Whitsett, Jeffrey A.

doi:10.1074/jbc.272.28.17327

Cited by 69 publications

(50 citation statements)

References 31 publications

(33 reference statements)

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“…In fact, several studies on phosphorylation of T/EBP and its relation to DNA binding and transcriptional activity have been reported. The results vary from phosphorylation by protein kinase C without any changes in binding affinity (40), to phosphorylation by protein kinase A and increase of DNA binding activity and transcription (41,42). Mammalian sterile 20-like 2 kinase (43) and extracellular signal-regulated kinase (44) were also shown to phosphorylate T/EBP.…”

Section: T/ebp/nkx21-dependent Il-10 Induction Of Ugrp1 Gene Expressionmentioning

confidence: 99%

Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1

Srisodsai

Kurotani

Chiba

et al. 2004

Journal of Biological Chemistry

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UGRP1 is a downstream target gene for homeodomain transcription factor T/EBP/NKX2.1, which is predominantly expressed in lung epithelial cells, and may play an anti-inflammatory role in lung inflammation. To understand the role of UGRP1 in inflammation, its expression was investigated in relation to cytokine signaling. In vivo experiments using mouse embryonic lung organ culture and intranasal administration of interleukin (IL) 10 revealed that constitutive expression of Ugrp1 mRNA is enhanced by IL-10. Increase of protein levels was also demonstrated by immunohistochemistry using embryonic lungs. This IL-10 induction of Ugrp1 gene expression occurs at the transcriptional level when examined using mouse embryonic lung primary cultures. Uteroglobin-related protein 1 (UGRP1) 1 was originally identified as a downstream target gene for homeodomain transcription factor T/EBP (thyroid-specific enhancer-binding protein), also called thyroid transcription factor-1 (TTF-1) or NKX2.1 (1). T/EBP regulates the expression of thyroid-and lung-specific genes including thyroglobulin (2), thyroid peroxidase (3, 4), thyrotropin receptor (5), and Na/I symporter (6) in the thyroid, and surfactant proteins A (7), B (8), and C (9), and Clara cell secretory protein (10) in the lung. T/EBP is expressed in brain, thyroid, and lung epithelium during embryogenesis and is essential for the genesis of these organs (11). In adult lung, the expression of T/EBP is confined to both the conducting airways and type II alveolar epithelial cells (12).UGRP1, officially named Secretoglobin gene family 3A2 (13), is a novel gene encoding a homodimeric secretory protein of ϳ10 kDa that is highly expressed in epithelial cells of the trachea, bronchus, and bronchioles (1). Based on our previous results, there is considerable evidence to suggest that UGRP1 may function in the regulation of the local immune response in the lung. First, the human UGRP1 gene is located on chromosome 5q31-q32, a region where one of the asthma susceptibility genes was assigned and genes coding for several Th2-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are located (13). Second, the UGRP1 amino acid sequence exhibits similarity to the UG/Clara cell secretory protein, which is known to function as an anti-inflammatory agent via inhibition of phospholipase A 2 (1). Third, a polymorphism (G/A) was identified in the human UGRP1 gene promoter that is associated with an increased risk of asthma in a Japanese population of adult asthmatic patients (14). Lastly, the mRNA level of Ugrp1 is decreased in inflamed mouse lungs, and returns to basal levels following dexamethasone treatment (1).IL-10 is a pleiotropic cytokine that was shown to mediate anti-inflammatory, immunosuppressive, and tissue protective functions. The known IL-10 signaling is through binding to specific receptors IL-10R1 and IL-10R2, which leads to activation of the JAK-STAT (Janus kinase-signal transducers and activators of transcription) signal transduction pathways (15). An anti-inflammatory role for I...

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Section: T/ebp/nkx21-dependent Il-10 Induction Of Ugrp1 Gene Expressionmentioning

confidence: 99%

Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1

Srisodsai

Kurotani

Chiba

et al. 2004

Journal of Biological Chemistry

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“…13.5 and p.c. 16 using 35 S-labeled cDNA probes as described previously (5). A 3.1-kilobase pair mouse GATA-6 cDNA template was utilized to generate 35 S-labeled probe, which was reduced to an average size of 200 base pairs by alkaline hydrolysis.…”

Section: Methodsmentioning

confidence: 99%

“…The glutathione-Sepharose 4B beads loaded with GST-GATA-6 retarded the 35 S-labeled TTF-1 protein (Fig. 4, lane 2), whereas the beads loaded with GST protein did not retard TTF-1 (Fig.…”

Section: Gata-6 and Ttf-1 Interact In Both Hela And Mle-15mentioning

confidence: 99%

“…ttf-1(Ϫ/Ϫ) mice have severely hypoplastic lung rudiments, lacking peripheral lung parenchyma at birth (10). Furthermore, TTF-1 is required for expression of surfactant proteins A-C and CCSP in the respiratory epithelium in vitro and in vivo (6,8,34,35). GATA-6 regulates ttf-1 gene transcription itself, binding and activating the ttf-1 gene promoter (27).…”

Section: Gata-4 Does Not Strongly Synergize With Ttf-1 In the Sp-c Prmentioning

confidence: 99%

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GATA-6 and Thyroid Transcription Factor-1 Directly Interact and Regulate Surfactant Protein-C Gene Expression

Liu

Glasser

Wan

et al. 2002

Journal of Biological Chemistry

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115

116

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“…Furthermore, the role of PKA-mediated phosphorylation in TTF-1 DNA binding activity was questioned in a later study (40) in which it was found that TTF-1 was not phosphorylated by PKA in vitro and that mutated forms of TTF-1 that could not be phosphorylated manifested normal levels of DNA binding and transcriptional activity in transfected HeLa cells. On the other hand, in a recent study, a PKA phosphorylation site near the N terminus (Thr 9 ) of TTF-1 was identified and found to be essential for PKA activation of the SP-B promoter in H441 cells, a lung adenocarcinoma cell line of Clara cell origin (44). The findings of the present study clearly indicate that cyclic AMP treatment of primary cultures of lung type II cells under conditions that increase SP-A gene transcription causes an increase in TTF-1 phosphorylation and DNA binding activity.…”

Section: Ttf-1 Regulation Of Sp-a Gene Expressionmentioning

confidence: 99%

Cyclic AMP-responsive Expression of the Surfactant Protein-A Gene Is Mediated by Increased DNA Binding and Transcriptional Activity of Thyroid Transcription Factor-1

Li¹,

Gao

Mendelson

1998

Journal of Biological Chemistry

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Protein Kinase A Activation of the Surfactant Protein B Gene Is Mediated by Phosphorylation of Thyroid Transcription Factor 1

Cited by 69 publications

References 31 publications

Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1

Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1

GATA-6 and Thyroid Transcription Factor-1 Directly Interact and Regulate Surfactant Protein-C Gene Expression

Cyclic AMP-responsive Expression of the Surfactant Protein-A Gene Is Mediated by Increased DNA Binding and Transcriptional Activity of Thyroid Transcription Factor-1

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