Effects of an aminosteroid inhibitor of phospholipase C-dependent processes on the TCR-mediated signal transduction pathway in human T cells

Abstract Background The filamentous fungus Trichoderma reesei is one of the best producers of cellulase and has been widely studied for the production of cellulosic ethanol and bio-based products. We previously reported that Mn2+ and N,N-dimethylformamide (DMF) can stimulate cellulase overexpression via Ca2+ bursts and calcium signalling in T. reesei under cellulase-inducing conditions. To further understand the regulatory networks involved in cellulase overexpression in T. reesei, we characterised the Mn2+/DMF-induced calcium signalling pathway involved in the stimulation of cellulase overexpression. Results We found that Mn2+/DMF stimulation significantly increased the intracellular levels of cAMP in an adenylate cyclase (ACY1)-dependent manner. Deletion of acy1 confirmed that cAMP is crucial for the Mn2+/DMF-stimulated cellulase overexpression in T. reesei. We further revealed that cAMP elevation induces a cytosolic Ca2+ burst, thereby initiating the Ca2+ signal transduction pathway in T. reesei, and that cAMP signalling causes the Ca2+ signalling pathway to regulate cellulase production in T. reesei. Furthermore, using a phospholipase C encoding gene plc-e deletion strain, we showed that the plc-e gene is vital for cellulase overexpression in response to stimulation by both Mn2+ and DMF, and that cAMP induces a Ca2+ burst through PLC-E. Conclusions The findings of this study reveal the presence of a signal transduction pathway in which Mn2+/DMF stimulation produces cAMP. Increase in the levels of cAMP activates the calcium signalling pathway via phospholipase C to regulate cellulase overexpression under cellulase-inducing conditions. These findings provide insights into the molecular mechanism of the cAMP–PLC–calcium signalling pathway underlying cellulase expression in T. reesei and highlight the potential applications of signal transduction in the regulation of gene expression in fungi.

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Nuclear Factor of Activated T Cells (NFAT) as a New Component of the Signal Transduction Pathway in Glioma Cells

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1998.71010134.x ◽

2002 ◽

Vol 71 (1) ◽

pp. 134-141 ◽

Cited By ~ 20

Author(s):

Grazyna Mosieniak ◽

Beata Pyrzynska ◽

Bozena Kaminska

Keyword(s):

Signal Transduction ◽

T Cells ◽

Signal Transduction Pathway ◽

Glioma Cells ◽

Nuclear Factor ◽

Transduction Pathway ◽

Activated T Cells

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Liposomal incorporation changes the effect of 1.25-dihydroxyvitamin D3 on the phospholipase C signal transduction pathway and the eicosanoid cascade on keratinocytes in vitro

Biochemical Pharmacology ◽

10.1016/0006-2952(96)02130-2 ◽

1996 ◽

Vol 51 (3) ◽

pp. 247-252 ◽

Cited By ~ 6

Author(s):

Kirsten Prüfer ◽

Gustav F. Jirikowski

Keyword(s):

Signal Transduction ◽

Phospholipase C ◽

Signal Transduction Pathway ◽

Transduction Pathway ◽

Dihydroxyvitamin D3

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Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms23020844 ◽

2022 ◽

Vol 23 (2) ◽

pp. 844

Author(s):

Myun Soo Kim ◽

Dongmin Park ◽

Sora Lee ◽

Sunyoung Park ◽

Kyung Eun Kim ◽

...

Keyword(s):

Signal Transduction ◽

T Cells ◽

Cd4 T Cells ◽

Signal Transduction Pathway ◽

Erythroid Differentiation ◽

Transduction Pathway ◽

Tcr Signaling ◽

Peripheral T Cells ◽

Signal Regulation

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.

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Characterization of phosphoinositide-specific phospholipase C in rat colonocyte membranes

Biochemical Journal ◽

10.1042/bj2920271 ◽

1993 ◽

Vol 292 (1) ◽

pp. 271-276 ◽

Cited By ~ 11

Author(s):

M J G Bolt ◽

B M Bissonnette ◽

R K Wali ◽

S C Hartmann ◽

T A Brasitus ◽

...

Keyword(s):

Signal Transduction ◽

Monoclonal Antibodies ◽

Phospholipase C ◽

Plasma Membranes ◽

Signal Transduction Pathway ◽

Protein S ◽

Transduction Pathway ◽

Intestinal Physiology ◽

Key Enzyme

The phosphoinositide signal transduction pathway mediates important processes in intestinal physiology, yet the key enzyme, phosphoinositide-specific phospholipase C (PI-PLC), is not well-characterized in the colon. PI-PLC activity was examined in rat colonic membranes using exogenous [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) as substrate, and beta-glycerophosphate to suppress degradation of substrate or product. The activity of membrane PI-PLC increased 6-fold with the addition of alamethicin, and a further 2-3-fold enhancement was observed with 10 microM guanosine 5′-[gamma-thio]triphosphate (GTP[S]), suggesting the involvement of G-protein(s). The effect of GTP[S] appeared to be specific, as up to 100 microM adenosine 5′-[gamma-thio]-triphosphate failed to stimulate PI-PLC activity, and guanosine 5′-[beta-thio]diphosphate inhibited activity. The response of membrane PI-PLC to Ca2+ was biphasic, while > 0.5 mM Mg2+ was inhibitory with or without GTP[S]. Comparable total PI-PLC activities and responses to GTP[S] and Ca2+ were observed in purified brush-border and basolateral membranes. Western immunoblots probed with monoclonal antibodies to PLC isoenzymes PLC-beta 1, -gamma 1 and -delta 1 demonstrated that these antipodal plasma membranes contain predominantly the PLC-delta 1 isoform, with small amounts of PLC-gamma 1 present but no detectable PLC-beta 1. PLC-gamma 1 was the major isoform detected in cytosol.

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