• Title/Summary/Keyword: Underlying mechanism

Search Result 1,222, Processing Time 0.024 seconds

A Natural L-Arginine Analog, L-Canavanine-Induced Apoptosis is Suppressed by Protein Tyrosine Kinase p56lck in Human Acute Leukemia Jurkat T Cells (인체 급성백혈병 Jurkat T 세포에 있어서 L-canavanine에 의해 유도되는 세포자살기전에 미치는 단백질 티로신 키나아제 p56lck의 저해 효과)

  • Park, Hae-Sun;Jun, Do-Youn;Woo, Hyun-Ju;Rue, Seok-Woo;Kim, Sang-Kook;Kim, Kyung-Min;Park, Wan;Moon, Byung-Jo;Kim, Young-Ho
    • Journal of Life Science
    • /
    • v.19 no.11
    • /
    • pp.1529-1537
    • /
    • 2009
  • To elucidate further the antitumor effects of a natural L-arginine analogue, L-canavanine, the mechanism underlying apoptogenic activity of L-canavanine and its modulation by protein tyrosine kinase $p56^{lck}$ was investigated in human Jurkat T cells. When the cells were treated with 1.25 to 2.5 mM L-canavanine for 36 h, several apoptotic events including mitochondrial membrane potential (${\Delta\Psi}m$) loss, activation of caspase-9, -3, -8, and -7, poly (ADP-ribose) polymerase (PARP) degradation, and DNA fragmentation were induced without alteration in the levels of Fas or FasL. These apoptotic changes were more significant in $p56^{lck}$-deficient Jurkat clone JCaM1.6 than in $p56^{lck}$-positive Jurkat clone E6.1. The L-canavanine-induced apoptosis observed in $p56^{lck}$-deficient JCaM1.6 cells was significantly reduced by introducing $p56^{lck}$ gene into JCaM1.6 cells by stable transfection. Treatment of JCaM1.6/lck cells with L-canavanine caused a transient 1.6-fold increase in the kinase activity of $p56^{lck}$. Both FADD-positive wild-type Jurkat T cell clone A3 and FADD-deficient Jurkat T cell clone I2.1 exhibited a similar susceptibility to the cytotoxicity of L-canavanine, excluding involvement of Fas/FasL system in triggering L-canavanine-induced apoptosis. The L-canavanine-induced apoptotic sub-$G_1$ peak and activation of caspase-3, -8, and -7 were abrogated by pan-caspase inhibitor (z-VAD-fmk), whereas L-canavanine-induced activation of caspase-9 was not affected. These results demonstrated that L-canavanine caused apoptosis of Jurkat T cells via the loss of ${\Delta\Psi}m$, and the activation of caspase-9, -3, -8, and -7, leading to PARP degradation, and that the $p56^{lck}$ kinase attenuated the ${\Delta\Psi}m$ loss and activation of caspases, and thus contributed as a negative regulator to L-canavanine-induced apoptosis.

Impact of Shortly Acquired IPO Firms on ICT Industry Concentration (ICT 산업분야 신생기업의 IPO 이후 인수합병과 산업 집중도에 관한 연구)

  • Chang, YoungBong;Kwon, YoungOk
    • Journal of Intelligence and Information Systems
    • /
    • v.26 no.3
    • /
    • pp.51-69
    • /
    • 2020
  • Now, it is a stylized fact that a small number of technology firms such as Apple, Alphabet, Microsoft, Amazon, Facebook and a few others have become larger and dominant players in an industry. Coupled with the rise of these leading firms, we have also observed that a large number of young firms have become an acquisition target in their early IPO stages. This indeed results in a sharp decline in the number of new entries in public exchanges although a series of policy reforms have been promulgated to foster competition through an increase in new entries. Given the observed industry trend in recent decades, a number of studies have reported increased concentration in most developed countries. However, it is less understood as to what caused an increase in industry concentration. In this paper, we uncover the mechanisms by which industries have become concentrated over the last decades by tracing the changes in industry concentration associated with a firm's status change in its early IPO stages. To this end, we put emphasis on the case in which firms are acquired shortly after they went public. Especially, with the transition to digital-based economies, it is imperative for incumbent firms to adapt and keep pace with new ICT and related intelligent systems. For instance, after the acquisition of a young firm equipped with AI-based solutions, an incumbent firm may better respond to a change in customer taste and preference by integrating acquired AI solutions and analytics skills into multiple business processes. Accordingly, it is not unusual for young ICT firms become an attractive acquisition target. To examine the role of M&As involved with young firms in reshaping the level of industry concentration, we identify a firm's status in early post-IPO stages over the sample periods spanning from 1990 to 2016 as follows: i) being delisted, ii) being standalone firms and iii) being acquired. According to our analysis, firms that have conducted IPO since 2000s have been acquired by incumbent firms at a relatively quicker time than those that did IPO in previous generations. We also show a greater acquisition rate for IPO firms in the ICT sector compared with their counterparts in other sectors. Our results based on multinomial logit models suggest that a large number of IPO firms have been acquired in their early post-IPO lives despite their financial soundness. Specifically, we show that IPO firms are likely to be acquired rather than be delisted due to financial distress in early IPO stages when they are more profitable, more mature or less leveraged. For those IPO firms with venture capital backup have also become an acquisition target more frequently. As a larger number of firms are acquired shortly after their IPO, our results show increased concentration. While providing limited evidence on the impact of large incumbent firms in explaining the change in industry concentration, our results show that the large firms' effect on industry concentration are pronounced in the ICT sector. This result possibly captures the current trend that a few tech giants such as Alphabet, Apple and Facebook continue to increase their market share. In addition, compared with the acquisitions of non-ICT firms, the concentration impact of IPO firms in early stages becomes larger when ICT firms are acquired as a target. Our study makes new contributions. To our best knowledge, this is one of a few studies that link a firm's post-IPO status to associated changes in industry concentration. Although some studies have addressed concentration issues, their primary focus was on market power or proprietary software. Contrast to earlier studies, we are able to uncover the mechanism by which industries have become concentrated by placing emphasis on M&As involving young IPO firms. Interestingly, the concentration impact of IPO firm acquisitions are magnified when a large incumbent firms are involved as an acquirer. This leads us to infer the underlying reasons as to why industries have become more concentrated with a favor of large firms in recent decades. Overall, our study sheds new light on the literature by providing a plausible explanation as to why industries have become concentrated.