Single-chain Tissue-type Plasminogen Activator Is a Substrate of Mouse Glandular Kallikrein 24

Matsui, Hitoshi; Takano, Naoharu; Moriyama, Akihiko; Takahashi, Takayuki

doi:10.2108/zsj.22.1105

Cited by 4 publications

(2 citation statements)

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“…Deregulated expression of Kallikreins has also been implicated in many cancer types [96-101]. The mouse Kallikreins Klk21, Klk24 and Klk27 have also been shown to be functionally active within the testes, both in degradation of the extra-cellular matrix and initiation of survival through degradation of Igf1bp3 [102-104]. Kallikrein proteins have been associated with angiogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Klk1, Klk21, Klk24 and Klk27 have been linked to Igf1-regulated tumour survival through degradation of the Igf binding protein Igfbp3 in humans. This prevents Igfbp3 from antagonizing Igf1-Igf1r interactions, allowing Igf1 to bind to its receptor and initiate survival via the Akt pathway [102-104,108]. Interestingly, the highest expression in a similar study from Frye et al using a basal keratinocyte model for MYC activation [90] was for the brain and skin protease gene Bssp1 , also known as Kallikrein 6 ( Klk6 ).…”

Section: Discussionmentioning

confidence: 99%

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Deciphering c-MYC-regulated genes in two distinct tissues

et al. 2011

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BackgroundThe transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively.ResultsConsistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins.ConclusionsActivation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19Arf/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19Arf by MYC in suprabasal keratinocytes may contribute.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deciphering c-MYC-regulated genes in two distinct tissues

et al. 2011

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Estrogen‐dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth

Rajapakse

Yamano

Ogiwara

et al. 2007

Molecular Reproduction Devel

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Tissue kallikrein mK1 is a serine protease involved in the generation of bioactive kinins for normal cardiac and arterial function in the mouse. In the present study, the tissue kallikrein gene Klk1, which codes for mK1, was shown to be one of the most prevalent of the Klk gene species in the uteri of adult mice, and its mRNA level was significantly higher at estrus than at diestrus. Klk1 mRNA expression was enhanced in the uteri of ovariectomized mice receiving estradiol-17beta treatment. Both endometrial epithelial and stromal cells isolated from the mice exhibited Klk1 expression at detectable levels when cultured in the presence of estradiol-17beta. mK1 was characterized using the recombinant active enzyme. mK1 had trypsin-like activity with a strong preference for Arg over Lys in the P1 position, and its activity was inhibited by typical serine protease inhibitors. Casein, gelatin, fibronectin, collagen type IV, and high-molecular-weight kininogen were degraded by mK1. The single-chain tissue-type plasminogen activator was converted to the two-chain form by mK1. In addition, mK1 degraded insulin-like growth factor binding protein-3. The present data suggest that mK1 may be implicated in the growth of uterine endometrial tissues during the proliferative phase.

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The Mouse Testis Is the Source of Various Serine Proteases and Serine Proteinase Inhibitors (SERPINs): Serine Proteases and SERPINs Identified in Leydig Cells Are under Gonadotropin Regulation

Odet

Verot

Magueresse-Battistoni

2006

Endocrinology

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The occurrence of various serine proteinases and serine proteinases inhibitors (SERPINs) was investigated by RT-PCR in whole testes of 1-, 3-, and 8-wk-old mice in crude and enriched germ cell fractions, mouse Leydig tumor cells (mLTC-1), and primary cultures of 3- and 8-wk-old enriched fractions of Leydig cells and 3-wk-old Sertoli cells. New members were identified in the testis protease repertoire. Within the Leydig repertoire, a PCR product was found for plasminogen activators urokinase plasminogen activator (uPA) and tissue plasminogen activator (8-wk-old cells), matriptase-2 (mLTC-1), kallikrein-21, SERPINA5, SERPINB2 (primary cultures), and serine peptidase inhibitor Kunitz type 2 (SPINT2). The gonadotropin regulation was explored by semiquantitative RT-PCR, using steroidogenic acute regulatory protein (StAR) as a positive control. Matriptase-2, kallikrein-21, SPINT2, and SERPINA5 were down-regulated, whereas uPA and its receptor were up-regulated by human chorionic gonadotropin (hCG) via cAMP in the mLTC-1 cells. Positive effects were observed transiently after 1-8 h of hCG exposure, and negative effects, first evidenced after 6 h, lasted 48 h. The hCG-induced effects were confirmed in primary cultures. In addition, SERPINB2 was augmented by hCG in primary cultures. Addition of either trypsin or protease inhibitors did not alter the hCG-induced surge of StAR. Because hCG regulated proteases and SERPINs (whereas testosterone did not), it could alter the proteolytic balance of Leydig cells and consequently the metabolism of extracellular matrix components. Therefore, even though a direct interplay between the early hCG-induced surge of uPA and StAR is unlikely, our data together with the literature suggest that extracellular matrix proteins alter Leydig cell steroidogenesis.

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Single-chain Tissue-type Plasminogen Activator Is a Substrate of Mouse Glandular Kallikrein 24

Cited by 4 publications

References 33 publications

Deciphering c-MYC-regulated genes in two distinct tissues

Deciphering c-MYC-regulated genes in two distinct tissues

Estrogen‐dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth

The Mouse Testis Is the Source of Various Serine Proteases and Serine Proteinase Inhibitors (SERPINs): Serine Proteases and SERPINs Identified in Leydig Cells Are under Gonadotropin Regulation

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