Inhibition of nuclear hormone receptor activity by calreticulin

Dedhar, Shoukat; Rennie, Paul S.; Shago, Mary; Hagesteijn, Chung-Yee Leung; Heng, Yang; Filmus, Jorge; Hawley, Robert G.; Bruchovsky, Nicholas; Cheng, Helen; Matusik, Robert J.; Giguère, Vincent

doi:10.1038/367480a0

Cited by 349 publications

(245 citation statements)

References 23 publications

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“…Smith, 1988. b Hoffman et al, 1987Lasek et al, 1983. c Smith andKoch, 1989;Opas et al, 1991;Burns et al, 1994;Dedhar et al, 1994. d Brunet et al, 1991.…”

Section: Resultsmentioning

confidence: 99%

Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

et al. 1995

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Behavioral, cellular and molecular changes were examined following axonal injury in the marine mollusc Aplysia californica. Unilateral nerve injury was performed by crushing the pleural-pedal connective and the peripheral pedal nerves innervating one side of the posterior body wall and the tail. The injury procedure severs the axons of the pleural sensory neurons resulting in the blockade of the tail-elicited siphon- withdrawal reflex. Partial reflex recovery is observed within 3 d and reaches 50% of the pretest value by six weeks postinjury. Retrograde staining of injured nerves combined with electrophysiological recordings from siphon motor neurons show that axons can regenerate through the crushed site and reconnect with the tail by three weeks postinjury. Moreover, the behavioral and electrophysiological measurements suggest that the contralateral sensory neurons may contribute to the early recovery of the siphon-withdrawal reflex. The levels of mRNAs coding for actin and calreticulin are elevated while the mRNAs coding for intermediate filament protein, sensorin A, FMRFamide are reduced in the ipsilateral pleural ganglia as detected by Northern blots. In the contralateral pleural ganglia, the levels of mRNAs coding for actin, sensorin A and FMRFamide are elevated. These molecular changes in both the ipsi- and contralateral sides are consistent with the hypothesis that both sides are participating in the behavioral recovery following unilateral axonal injury.

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“…Smith, 1988. b Hoffman et al, 1987Lasek et al, 1983. c Smith andKoch, 1989;Opas et al, 1991;Burns et al, 1994;Dedhar et al, 1994. d Brunet et al, 1991.…”

Section: Resultsmentioning

confidence: 99%

Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

et al. 1995

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“…It has three distinct domains: the amino terminal N-domain, the proline-rich P-domain, and the carboxyl-terminal C-domain (16 -18). The N-domain binds to the protein sequence KxFF[K/R]R, which is found in the cytoplasmic domain of the ␣-subunit of integrins (19) and in several steroid hormone receptors, including the glucocorticoid receptor (20), the androgen receptor, and the retinoic acid receptor (21). Perforin contains the amino acid sequence KVFF (residues 439 -442), which represents part of this calreticulin-binding motif.…”

Section: Perforin Lytic Activity Is Controlled By Calreticulinmentioning

confidence: 99%

Perforin Lytic Activity Is Controlled by Calreticulin

Fraser

Karimi

Michalak

et al. 2000

The Journal of Immunology

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The components within cytotoxic lymphocyte granules are responsible for a significant fraction of T and NK cell-mediated death. Perforin is stored in these granules together with calreticulin. Calreticulin has long been recognized as a chaperone protein of the endoplasmic reticulum (ER) and is the only resident ER protein to be found in the cytotoxic granules. Here we implicate a role for calreticulin in killing and report that it controls osmotic lysis mediated by purified perforin. Calreticulin, at a concentration of 2.2 × 10−7 M, completely blocked perforin-mediated lysis. Inhibition was stable and held over 5 h. Recombinant calreticulin, at a concentration of 8.8 × 10−7 M, also blocked lysis, indicating the inhibition was due to calreticulin and not a copurifying protein in the native calreticulin preparations. Using calreticulin domain fragments (expressed as GST fusion proteins), we found inhibitory activity in the high-capacity calcium-binding C-domain, which does not bind perforin. The N- or P-domains, which can bind perforin, were unable to block lysis. The inhibition of lysis was independent of granzyme inactivation or the ability of calreticulin to sequester calcium. Our data indicate that calreticulin regulation of perforin-mediated lysis probably occurs without direct interaction with perforin. We propose a novel model in which calreticulin stabilizes membranes to prevent polyperforin pore formation.

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“…It was first described as a calcium-binding protein of the sarcoplasmic reticulum of smooth-muscle cells [40,41]. Calreticulin has subsequently been shown (i) to possess a calcium-binding function [42] and chaperone activity [43] in the endoplasmic reticulum ; (ii) to have RNA binding activity [44] ; and (iii) to modify gene expression by binding to nuclear-hormone receptors [45,46]. It has also been shown that calreticulin can bind to the KXGFFKR motif within the α subunits of integrins [27] (where X indicates any residue), and that antisense oligonucleotide-mediated downregulation of calreticulin expression inhibits integrin-mediated adhesion of PC-3 and Jurkat cells [29].…”

Section: Discussionmentioning

confidence: 99%

Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events

Coppolino

Dedhar

1999

Biochemical Journal

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As transmembrane heterodimers, integrins bind to both extracellular ligands and intracellular proteins. We are currently investigating the interaction between integrins and the intracellular protein calreticulin. A prostatic carcinoma cell line (PC-3) was used to demonstrate that calreticulin can be found in the α3 immunoprecipitates of cells plated on collagen type IV, but not when plated on vitronectin. Conversely, αv immunoprecipitates contained calreticulin only when cells were plated on vitronectin, i.e. not when plated on collagen IV. The interactions between these integrins and calreticulin were independent of actin cytoskeleton assembly and were transient, being maximal approx. 10-30 min after the cells came into contact with the substrates prior to complete cell spreading and formation of firm adhesive contacts. We demonstrate that okadaic acid, an inhibitor of intracellular serine/threonine protein phosphatases, inhibited the α3β1-mediated adhesion of PC-3 cells to collagen IV and the α2β1-mediated attachment of Jurkat cells to collagen I. This inhibition by okadaic acid was accompanied by inhibition of the ligand-specific interaction of calreticulin with the respective integrins in the two cell types. Additionally, we found that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) resulted in prolongation of the calreticulin-integrin interaction, and enhancement of PC-3 cell attachment to collagen IV. We conclude that calreticulin interacts transiently with integrins during cell attachment and spreading. This interaction depends on receptor occupation, is ligand-specific, and can be modulated by protein phosphatase and MEK activity.

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Inhibition of nuclear hormone receptor activity by calreticulin

Cited by 349 publications

References 23 publications

Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

Perforin Lytic Activity Is Controlled by Calreticulin

Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events

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