Connexins, gap junctional intercellular communication and kinases

Cruciani, Véronique; Mikalsen, Svein‐Ole

doi:10.1016/s0248-4900(02)00014-x

Cited by 86 publications

(69 citation statements)

References 141 publications

(161 reference statements)

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“…Numerous studies show that phosphorylation plays a key role in connexin expression and function, as well as overall gap junction permeability (Cruciani and Mikalsen, 2002;Lampe and Lau, 2000;Lowenstein, 1985;Musil and Goodenough, 1991). For example, phosphorylation of Cx43 on Ser368 by protein kinase C (PKC) decreases gap junctional communication by reducing single channel conductance (Richards et al, 2004).…”

Section: ) Discussionmentioning

confidence: 99%

“…Gap junction channels are dynamic macromolecular complexes capable of opening and closing in response to a multitude of stimuli including pH, divalent cations, signaling molecules, and phosphorylation (De Mello, 1988, Saez et al, 2003. Kinases and phosphorylation of connexins are involved in the regulation of intercellular communication at all levels ranging from the expression of connexin genes to the degradation of gap junction channels (Cruciani and Mikalsen, 2002;Lampe and Lau, 2000). Previous work suggests that viruses may alter tyrosine protein kinase activity (Fletcher et al, 1987) which phosphorylates tyrosine residues in the gap junctional protein connexin-43 (Cx43) ( Brissette et al, 1991, Crow et al, 1990Filson et al, 1990; Goldstein et al, 1991, Warn-Cramer andLau, 2004).…”

Section: ) Introductionmentioning

confidence: 99%

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Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication

et al. 2007

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SUMMARYIn rat liver epithelial (WB) cells, the protein kinase C inhibitor H7 blocked gap junctional intercellular communication (GJIC) and reduced virus infectivity. Octanol, 18-beta-glycyrrhetinic acid, and staurosporine, agents that reduce GJIC, had no effect upon virus infectivity. Previous studies demonstrated that herpes simplex virus-type 2 (HSV-2) infection was accompanied by attenuated GJIC. Of agents tested, only H7 reduced plaque forming unit (pfu) ability in a dose-dependent manner with 100% plaque reduction at 40 μM without evidence of cytotoxicity. Dye transfer indicated that H7 decreased GJIC, although Western blotting revealed that it did not alter phosphorylation of the gap junction protein, connexin 43 (Cx43). Using indirect immunofluorescence, Cx43 was found to localize in membrane plaques in uninfected cells and H-7 did not alter this distribution. However, Cx43 was lost from the membrane at 24 hrs in both H-7 treated and untreated cells infected with HSV-2. Viral infection increased serine phosphorylation, particularly in the nuclear region, and this effect was reduced following H-7 treatment. Thus, H-7 attenuated both GJIC and infectivity of HSV-2 in WB cells but the anti-viral effects were due to reduced nuclear protein phosphorylation rather than alterations in phosphorylation or localization of Cx43. KeywordsGap junctions; Connexin 43; protein kinase C; H7; HSV-2 1) INTRODUCTIONIt has long been known that certain RNA and tumor viruses decrease gap junctional communication among infected cells (Atkinson et al., 1981;Crow et al., 1990;Danave et al., 1994;Ennaji et al., 1995;Faccini et al., 1996, Jou et al., 1995. Recent studies have shown electrophysiologically that down-regulation of gap junctions by herpes simplex virus-type 2 (HSV-2) begins before viral DNA replication, and long before morphological signs of infection (Fischer et al., 2001). In addition, Musee et al. (2002) demonstrated that antiviral agents affect electrical coupling in HSV-2 infected cells in different ways, depending on the mechanism of action of the agent. However, it was not clear if GJIC down-regulation was initiated by the infected cells or by their surrounding uninfected neighbors. If the latter, drugs that reduce GJIC might protect neighboring cells from infection.* To whom all correspondence should be addressed: Phone -(610)-436-2985, Fax -(610)-436-2183, e-mail-mknabb@wcupa.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. How HSV-2 induces gap junctional down-regulation is unknown although both viral-or cellmediated mechanisms are possible. Gap junction channels are...

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Section: ) Discussionmentioning

confidence: 99%

Section: ) Introductionmentioning

confidence: 99%

Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication

et al. 2007

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“…The variety of Cx43 expression was confirmed with Western blotting analysis that showed four different intensity bands, each corresponding to the nonphosphorylated form and the three phosphorylated isoforms of Cx43. [22][23][24] . Several studies have documented that dephosphorylation of Cx43 is associated with Cx43 gap junction degradation.…”

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confidence: 99%

Reduced expression of the gap junction protein Connexin 43 in keratoconus

Gatzioufas

Charalambous

Thanos

2007

Eye

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Purpose The purpose of the present study was to examine whether keratoconus, which is a bilateral noninflammatory corneal ectasia with multifactorial aetiology, shows altered expression of Connexin (Cx43). Cx43 is an important gap junction protein that contributes crucially to epithelial and stromal integrity of cornea. Methods Eight keratoconic human corneal buttons were examined with immunohistochemistry and Western blotting and compared with eight normal human corneal buttons, to unravel changes in Cx43 expression. Results All normal corneas exhibited similar epithelial Cx43 expression patterns, with the protein located in the basal epithelial layer. In contrast, some keratoconic corneas showed an altered pattern of immunostaining and Western blotting confirmed a decreased expression of Cx43 in keratoconic corneas. Conclusions Our results indicate that a decrease in Cx43 amount together with functional alteration of the protein is associated with keratoconus pathophysiology However, these changes apply only to some of the corneas examined and may not generally account for the development of keratoconus.

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“…In contrast to the response to EGF described above, GJIC increased in a human kidney cell line after exposure to EGF [18]. This also appears to be dependent on the ERK pathway, but protein synthesis was needed [3]. It is presently unknown as to why two cell types are stimulated with the same growth factors, utilizing the same transduction pathway, and having the same Cx protein, yet have opposite responses with regard to GJIC.…”

Section: Discussionmentioning

confidence: 78%

“…The p38 group kinase has been found to be involved in inflammation, cell growth, cell differentiation, the cell cycle, and cell death [14]. Therefore, MAPKs might play important roles in the regulation of GJIC by phosphorylation of Cxs [2,3]. MAPKs, which include ERK, c-Jun N-terminal kinase (JNK), and the p38 subfamilies, are important regulatory proteins that transduce various extracellular signals into intracellular events [13].…”

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confidence: 99%

Expression of MAP Kinases and Connexins in the Differentiation of Rat Mammary Epithelial Cells

Seo

Park

Yang

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. Gap junctional intercellular communication (GJIC) is involved in the regulation of many cellular processes. MAP kinases are known to affect GJIC and phosphorylation of connexin (Cx). MAP kinases can also be a regulator of cell proliferation and growth. This study was undertaken to show the relevance between expression patterns of Cxs and MAP kinases in rat mammary epithelial cells (RMECs). In order to characterize the RMECs, they were stained with Peanut lectin, which indicates most alveolar epithelial cells, and Thy-1.1 was used as a marker of luminal epithelial cells or myoepithelial cells, respectively. We studied the expression patterns of major gap junction proteins, Cx 26, 32, and 43 in RMECs. Western blot analysis demonstrated that Cx26 gradually decreased from day 2, while Cx32 was expressed constantly from day 1 to 14. Cx43 dramatically increased on day 5 and decreased thereafter. The expression patterns and phosphorylation of ERK1/2 and JNK were similar to Cx43, but expression of p38 was like that of Cx32. These results showed that the MAP kinases that comprise ERK1/2, p38, and JNK were involved in regulation of Cxs. Our data suggests that GJIC plays an important role during rat mammary differentiation and that MAP kinases may be closely related functionally to regulate the gap junction. KEY WORDS: connexin, gap junction, MAP kinase, rat mammary epithelial cell.

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Connexins, gap junctional intercellular communication and kinases

Cited by 86 publications

References 141 publications

Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication

Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication

Reduced expression of the gap junction protein Connexin 43 in keratoconus

Expression of MAP Kinases and Connexins in the Differentiation of Rat Mammary Epithelial Cells

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