Suppression of Ultraviolet Irradiation-induced Apoptosis by Overexpression of Focal Adhesion Kinase in Madin-Darby Canine Kidney Cells

Chan, Po Chao; Lai, Jui Fen; Cheng, Chun-Yuan; Tang, Ming Jer; Chiu, Chia Chieh; Chen, Hong Chen

doi:10.1074/jbc.274.38.26901

Cited by 102 publications

(96 citation statements)

References 49 publications

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“…PI3K proteins are subdivided into three major groups, and group I PI3K has been identified as a downstream effector of both receptor and non-receptor tyrosine kinases (16 (20). PI3K has been shown to act downstream of FAK in cell migration and survival (21)(22)(23). In this paper, we report the activation of PI3K/Akt signaling in E. coli K1 invasion of HBMECs and demonstrate that PI3K interaction with FAK is required for the activation of PI3K/Akt signaling in this process.…”

Section: Invasion Of Brain Microvascular Endothelial Cells (Bmec)mentioning

confidence: 82%

Phosphatidylinositol 3-Kinase Activation and Interaction with Focal Adhesion Kinase in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

Reddy¹,

Prasadarao²,

Wass³

et al. 2000

Journal of Biological Chemistry

127

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Invasion of brain microvascular endothelial cells (BMEC) is a prerequisite for successful crossing of the blood-brain barrier by Escherichia coli K1. We have previously demonstrated the requirement of cytoskeletal rearrangements and activation of focal adhesion kinase (FAK) in E. coli K1 invasion of human BMEC (HBMEC).The current study investigated the role of phosphatidylinositol 3-kinase (PI3K) activation and PI3K interaction with FAK in E. coli invasion of HBMEC. PI3K inhibitor LY294002 blocked E. coli K1 invasion of HBMEC in a dose-dependent manner, whereas an inactive analogue LY303511 had no such effect. In HBMEC, E. coli K1 increased phosphorylation of Akt, a downstream effector of PI3K, which was completely blocked by LY294002. In contrast, non-invasive E. coli failed to activate PI3K. Overexpression of PI3K mutants ⌬p85 and catalytically inactive p110 in HBMEC significantly inhibited both PI3K/Akt activation and E. coli K1 invasion of HBMEC. Stimulation of HBMEC with E. coli K1 increased PI3K association with FAK. Furthermore, PI3K/Akt activation was blocked in HBMEC-overexpressing FAK dominant-negative mutants (FRNK and Phe397FAK). These results demonstrated the involvement of PI3K signaling in E. coli K1 invasion of HBMEC and identified a novel role for PI3K interaction with FAK in the pathogenesis of E. coli meningitis.In neonates, Escherichia coli is the most common Gramnegative bacterium that causes meningitis, a serious disease affecting the central nervous system. The most distressing aspect of neonatal Gram-negative meningitis is high morbidity and mortality despite advances in antimicrobial chemotherapy and supportive care. Increased understanding of the pathogenesis and pathophysiology of this disease can lead to improved outcome. Intravascular survival and penetration of the bloodbrain barrier by circulating bacteria represent the most critical events in the development of bacterial meningitis (1). Invasion of brain microvascular endothelial cells (BMEC)1 is a requirement for E. coli crossing of the blood-brain barrier, and it involves attachment of E. coli to BMEC through interaction of bacterial ligands with corresponding receptors present on BMEC cell surface (2). Several E. coli determinants (OmpA, IbeA, Ibe B, and YijP) involved in the invasion of BMEC have been identified (3-6). Receptors on the surface of BMEC for two of these E. coli determinants (OmpA and IbeA) have been characterized biochemically (7,8). We have recently demonstrated that E. coli invasion of BMEC occurs via a zipper-like mechanism and requires cytoskeletal rearrangements in the host cell (9). We have further characterized in BMEC that E. coli K1 induces tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, a cytoskeletal protein known to associate with FAK (10). Furthermore, using FAK dominantnegative mutants we have shown that FAK kinase activity and its autophosphorylation site tyrosine 397 (Tyr-397) are critical for E. coli K1 invasion of HBMEC (10). These results establish that FAK signaling is e...

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Section: Invasion Of Brain Microvascular Endothelial Cells (Bmec)mentioning

confidence: 82%

Phosphatidylinositol 3-Kinase Activation and Interaction with Focal Adhesion Kinase in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

Reddy¹,

Prasadarao²,

Wass³

et al. 2000

Journal of Biological Chemistry

127

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“…12 Cleavage of FAK abrogates its ability to bind to paxillin but not to p130Cas. 13 FAK undergoes sequential proteolysis at two sites (DQTD 772 and VSWD 704 ), generating a fragment containing an intact kinase domain and another fragment containing the focal adhesion targeting (FAT) domain. 14,15 That the choice of caspase cleavage sites may be of critical importance is based on several interesting observations.…”

Section: (I) Kinases That Regulate Cell Morphologymentioning

confidence: 99%

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

2000

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Caspases are the major executioners of cell death, serving as molecular guillotines to behead many proteins required for maintenance of cellular homeostasis. Identification of caspase substrates has taken on increasing importance as we attempt to better understand the molecular mechanisms involved in regulating the struggle between life and death. Many caspase substrates have been described and include RNA binding proteins such as La and U1-70 kD, structural proteins such as keratin and nuclear lamins, and transcription factors or their regulatory proteins that include IkB, SP1, and SREBP. Kinases and other signaling proteins are perfectly suited to regulate life and death decisions in response to cellular stressors and have only recently been identified as important caspase substrates. Here we review the current status of signaling pathways that are activated, inactivated or dysregulated by proteases such as caspases and calpain to control entry into apoptosis. The emerging concept that some caspase pathways may be inhibited by cellular and viral apoptosis inhibitory proteins while other caspase pathways are preserved suggests that a subset of these kinases may exist as cleaved`isoforms' in cells that are not destined to perish. By acting as executioners and as important`molecular sensors' of the degree of cellular injury, the signaling proteins described in this review are strong candidates to mediate downstream events, both in condemned and in viable cells.

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“…The C-terminal cleavage fragment of FAK, which resembles a natural variant of FRNK (FAK-related non-kinase), inhibits FAK activity by preventing its localization at focal adhesions (11), where FAK-mediated survival signals are transduced via tyrosine phosphorylation of p130 cas and subsequent coupling of p130 cas and Crk. In that regard, overexpression of p130 protects cells from apoptosis (12)(13)(14), whereas inhibition of p130 cas phosphorylation or overexpression of dominant negative forms of p130 cas (15)(16)(17) induces apoptosis. Moreover, caspase-mediated cleavage of p130 cas is closely associated with apoptosis induced by a variety of agents (4,5,10,14,16,18,19).…”

mentioning

confidence: 99%

The 31-kDa Caspase-generated Cleavage Product of p130 Functions as a Transcriptional Repressor of E2A in Apoptotic Cells

Kim

Kook

Kim

et al. 2004

Journal of Biological Chemistry

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In response to integrin receptor binding to the extracellular matrix, the multidomain docking protein p130 cas (Crk-associated substrate) activates various signaling cascades modulating such cellular processes as proliferation, migration, and apoptosis. During apoptosis, caspase-mediated cleavage of p130 cas generated a C-terminal 31-kDa fragment (31-kDa) and promoted morphological changes characteristic of apoptosis, including loss of focal adhesions, cell rounding, and nuclear condensation and fragmentation. By contrast, a p130 cas D748E mutant, which was unable to produce 31-kDa, attenuated the disassembly of focal adhesions at the bottom of the cell. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id proteins than with basic HLH proteins, which enabled heterodimerization with E2A. Once coupled to E2A, 31-kDa was translocated to the cell nucleus, where it inhibited E2A-mediated p21 Waf1/Cip1 transcription. Moreover, overexpression of 31-kDa led to cell death that could be inhibited by treatment with the caspase inhibitor ZVAD-fluoromethyl ketone or by ectopic expression of E2A or p21 Waf1/Cip1 . These data suggest that during etoposide-induced apoptosis, 31-kDa promotes caspase-mediated cell death by inhibiting E2A-mediated activation of p21 Waf1/Cip1 transcription.

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Suppression of Ultraviolet Irradiation-induced Apoptosis by Overexpression of Focal Adhesion Kinase in Madin-Darby Canine Kidney Cells

Cited by 102 publications

References 49 publications

Phosphatidylinositol 3-Kinase Activation and Interaction with Focal Adhesion Kinase in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

Phosphatidylinositol 3-Kinase Activation and Interaction with Focal Adhesion Kinase in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

The 31-kDa Caspase-generated Cleavage Product of p130 Functions as a Transcriptional Repressor of E2A in Apoptotic Cells

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