Spi-1: an hepatic serine protease inhibitor regulated by GH and other hormones

Warren, Wesley C.; Munie, Grace E.; Glenn, Kevin C.

doi:10.1016/0303-7207(93)90232-9

Cited by 10 publications

(4 citation statements)

References 27 publications

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“…The SPI 2.1 gene is expressed principally in the liver. It is not expressed in a variety of other tissues expressing receptors for growth hormone, nor is its expression stimulated by other cytokines, such as prolactin, which are capable of activating STAT 5 (Warren et al, 1993). In addition to the region containing the STAT responsive element the SPI 2.1 promoter has been shown to contain other growth hormone responsive regions (Le-Cam et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Specificity of transcription enhancement via the STAT responsive element in the serine protease inhibitor 2.1 promoter

Wood

Slíva

Lobie

et al. 1997

Molecular and Cellular Endocrinology

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Section: Discussionmentioning

confidence: 99%

Specificity of transcription enhancement via the STAT responsive element in the serine protease inhibitor 2.1 promoter

Wood

Slíva

Lobie

et al. 1997

Molecular and Cellular Endocrinology

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“…Prolactin was not able to stimulate expression of Spi 2.1 and/or insulin-like growth factor I mRNA under conditions that produced a GH response (29,30). Although GH can activate Stat5 (7), it does not induce transcription of a ␤-casein construct in transfection assays even if Stat5 is cotransfected along with GH receptor (23).…”

Section: Fig 5 Ghinf Is Distinct From Stat1 and Stat3mentioning

confidence: 96%

Growth Hormone Induction of Hepatic Serine Protease Inhibitor 2.1 Transcription Is Mediated by a Stat5-related Factor Binding Synergistically to Two γ-Activated Sites

Bergad

Shih

Towle

et al. 1995

Journal of Biological Chemistry

114

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A growth hormone (GH)-inducible nuclear factor (GHINF) from rat liver has been purified to near homogeneity. On SDS-polyacrylamide gel electrophoresis and UV-cross-linking, a major band of mass ϳ93 kDa and a minor band of ϳ70 kDa are detected in the purified fraction. DNase I footprinting using purified GHINF yields a protected region of ؊149/؊115 on the rat serine protease inhibitor 2.1 (Spi 2.1) promoter encompassed within the growth hormone response element (GHRE). Mutational analysis demonstrated that GHINF binds synergistically to two ␥-interferon-activated sites (GAS) within the GHRE, with the 3 element being the pivotal binding domain. Functional assays show that both GAS elements are necessary for full GH response. GHINF has no immunoreactivity with either a C-terminal Stat1 antibody or an N-terminal Stat3 antibody, while cross-reacting with a C-terminal Stat5 monoclonal antibody. GHINF will bind to two GAS elements from the Stat5 binding region of the ␤-casein gene. These studies indicate that GHINF is a Stat5-related factor binding synergistically to two GAS elements to activate Spi 2.1 transcription.Great strides have been made in the last year toward understanding the mechanisms of cytokine and growth factor signal transduction. These extracellular signaling proteins include growth hormone (GH), 1 prolactin, interleukins (IL), interferons, granulocyte-macrophage colony stimulating factor, and colony stimulating factor 1. The binding of these polypeptides to their specific surface receptors in target cells is followed by a cascade of events activating the Jak-STAT pathway. In this pathway, the Janus kinase (Jak) family of tyrosine kinases, known to be associated with these receptors, are activated and tyrosine-phosphorylated. These kinases, in turn, presumably activate a family of latent cytoplasmic proteins known as signal transducers and activators of transcription (STAT), through phosphorylation of tyrosine residues. The activated STAT proteins are then translocated to the nucleus where they, by themselves or in combination with otherwise weak DNA-binding proteins, bind to specific response elements on responsive genes and activate transcription (1). Six of these STAT proteins have been identified to date. Some of the STAT proteins are highly specific in their response to individual cytokines (e.g. Stat2 for interferon-␣), while others appear to be involved in multiple pathways (2). The STAT proteins recognize response elements that share homology with the ␥-interferon activation site (GAS) recognized by Stat1 (1).The involvement of Jak-STAT pathways in GH signal transduction has been evidenced recently. Jak2 has been shown to be associated with GH receptors following GH binding with phosphorylation of both Jak2 and the GH receptor and subsequent activation of signal transduction (3). Further, it has been observed that GH treatment appears to activate several STAT proteins resulting in their phosphorylation. This has been noted both in cultured cell systems (4 -7) and in liver (8, 9), a known targe...

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“…In mammals, these include several proto-oncogenes (Yoon et al 1990;Triest et al 1995), some protease inhibitors (Yoon et al 1987;Warren et al 1993), steroid hydroxylases (Wells et al 1994;Subramanian et al 1995) and insulin-like growth factors (Bichell et al 1992;Gronowski and Rotwein 1995). Changes in the expression of these genes therefore provides markers of GH action in GH target sites.…”

Section: Introductionmentioning

confidence: 95%

Growth hormone (GH) action in early embryogenesis: expression of a GH-response gene in sites of GH production and action

Harvey¹,

Lavelin

Pines

2001

Anatomy and Embryology

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Growth hormone (GH) may act as a local growth factor in early embryonic development, since GH- and GH-receptor (GHR) immunoreactivity is present in all tissues and most cells of embryonic chicks during organogenesis. However, as GHR-immunoreactivity could, alternatively, reflect the presence of GH-binding proteins (GHBPs) rather than authentic receptors linked to signal transduction mechanisms, GHR immunoreactivity may not be indicative of GH target sites. The possibility that GH may act as an autocrine or paracrine factor during embryogenesis was therefore assessed in the present study by determining the presence and cellular localization of mRNA for a GH-responsive gene. The mechanism of GH action involves the induction of a number of specific GH-response genes. In chickens a novel GH-responsive gene (GHRG-1) has been identified as a marker of GH action. In situ hybridization, using a 860 bp probe for GHRG-1 mRNA, demonstrated widespread expression of the GHRG-1 gene in embryonic tissues known to contain GH- and GHR-immunoreactivity (e.g. in the spinal cord, skin, heart, liver, muscle, bone and lung). GHRG-1 mRNA was not, however, present in all cells of each tissue. It was, furthermore, not present in subepithelial cells of the esophagus and bronchus and was lacking in many spinal cord ependyma, which are also known to lack GH immunoreactivity. These results therefore support the possibility that GH acts as an autocrine/paracrine factor during early chick embryogenesis, which was hitherto thought to be a "growth-without-GH" syndrome.

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Spi-1: an hepatic serine protease inhibitor regulated by GH and other hormones

Cited by 10 publications

References 27 publications

Specificity of transcription enhancement via the STAT responsive element in the serine protease inhibitor 2.1 promoter

Specificity of transcription enhancement via the STAT responsive element in the serine protease inhibitor 2.1 promoter

Growth Hormone Induction of Hepatic Serine Protease Inhibitor 2.1 Transcription Is Mediated by a Stat5-related Factor Binding Synergistically to Two γ-Activated Sites

Growth hormone (GH) action in early embryogenesis: expression of a GH-response gene in sites of GH production and action

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