STIM1 knockout enhances PDGF-mediated Ca2+ signaling through upregulation of the PDGFR–PLCγ–STIM2 cascade

Tzu Yu Huang, Yi Hsin Lin, Heng Ai Chang, Tzu Ying Yeh, Ya Han Chang, Yi Fan Chen, Ying Chi Chen, Chun-Chun Li, Wen Tai Chiu

Research output: Contribution to journalArticle

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Abstract

Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE. In this study, wild-type and STIM1 knockout mouse embryonic fibroblasts (MEF) cells were used to investigate the role of STIM1 in PDGF-induced Ca2+ oscillation and its functions in MEF cells. The unexpected findings suggest that STIM1 knockout enhances PDGFR–PLCγ–STIM2 signaling, which in turn increases PDGF-BB-induced Ca2+ elevation. Enhanced expressions of PDGFRs and PLCγ in STIM1 knockout cells induce Ca2+ release from the ER store through PLCγ–IP3 signaling. Moreover, STIM2 replaces STIM1 to act as the major ER Ca2+ sensor in activating SOCE. However, activation of PDGFRs also activate Akt, ERK, and JNK to regulate cellular functions, such as cell migration. These results suggest that alternative switchable pathways can be observed in cells, which act downstream of the growth factors that regulate Ca2+ signaling.

Original languageEnglish
Article number1799
JournalInternational journal of molecular sciences
Volume19
Issue number6
DOIs
Publication statusPublished - 2018 Jun 18

Fingerprint

Platelet-Derived Growth Factor
Platelets
platelets
cascades
Up-Regulation
Platelet-Derived Growth Factor Receptors
Molecules
Phospholipase C gamma
fibroblasts
Fibroblasts
molecules
entry
interactions
cells
knockout mice
Knockout Mice
Cell Movement
Stromal Interaction Molecule 1
Intercellular Signaling Peptides and Proteins
stimulation

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Huang, Tzu Yu ; Lin, Yi Hsin ; Chang, Heng Ai ; Yeh, Tzu Ying ; Chang, Ya Han ; Chen, Yi Fan ; Chen, Ying Chi ; Li, Chun-Chun ; Chiu, Wen Tai. / STIM1 knockout enhances PDGF-mediated Ca2+ signaling through upregulation of the PDGFR–PLCγ–STIM2 cascade. In: International journal of molecular sciences. 2018 ; Vol. 19, No. 6.
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abstract = "Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE. In this study, wild-type and STIM1 knockout mouse embryonic fibroblasts (MEF) cells were used to investigate the role of STIM1 in PDGF-induced Ca2+ oscillation and its functions in MEF cells. The unexpected findings suggest that STIM1 knockout enhances PDGFR–PLCγ–STIM2 signaling, which in turn increases PDGF-BB-induced Ca2+ elevation. Enhanced expressions of PDGFRs and PLCγ in STIM1 knockout cells induce Ca2+ release from the ER store through PLCγ–IP3 signaling. Moreover, STIM2 replaces STIM1 to act as the major ER Ca2+ sensor in activating SOCE. However, activation of PDGFRs also activate Akt, ERK, and JNK to regulate cellular functions, such as cell migration. These results suggest that alternative switchable pathways can be observed in cells, which act downstream of the growth factors that regulate Ca2+ signaling.",
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STIM1 knockout enhances PDGF-mediated Ca2+ signaling through upregulation of the PDGFR–PLCγ–STIM2 cascade. / Huang, Tzu Yu; Lin, Yi Hsin; Chang, Heng Ai; Yeh, Tzu Ying; Chang, Ya Han; Chen, Yi Fan; Chen, Ying Chi; Li, Chun-Chun; Chiu, Wen Tai.

In: International journal of molecular sciences, Vol. 19, No. 6, 1799, 18.06.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - STIM1 knockout enhances PDGF-mediated Ca2+ signaling through upregulation of the PDGFR–PLCγ–STIM2 cascade

AU - Huang, Tzu Yu

AU - Lin, Yi Hsin

AU - Chang, Heng Ai

AU - Yeh, Tzu Ying

AU - Chang, Ya Han

AU - Chen, Yi Fan

AU - Chen, Ying Chi

AU - Li, Chun-Chun

AU - Chiu, Wen Tai

PY - 2018/6/18

Y1 - 2018/6/18

N2 - Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE. In this study, wild-type and STIM1 knockout mouse embryonic fibroblasts (MEF) cells were used to investigate the role of STIM1 in PDGF-induced Ca2+ oscillation and its functions in MEF cells. The unexpected findings suggest that STIM1 knockout enhances PDGFR–PLCγ–STIM2 signaling, which in turn increases PDGF-BB-induced Ca2+ elevation. Enhanced expressions of PDGFRs and PLCγ in STIM1 knockout cells induce Ca2+ release from the ER store through PLCγ–IP3 signaling. Moreover, STIM2 replaces STIM1 to act as the major ER Ca2+ sensor in activating SOCE. However, activation of PDGFRs also activate Akt, ERK, and JNK to regulate cellular functions, such as cell migration. These results suggest that alternative switchable pathways can be observed in cells, which act downstream of the growth factors that regulate Ca2+ signaling.

AB - Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE. In this study, wild-type and STIM1 knockout mouse embryonic fibroblasts (MEF) cells were used to investigate the role of STIM1 in PDGF-induced Ca2+ oscillation and its functions in MEF cells. The unexpected findings suggest that STIM1 knockout enhances PDGFR–PLCγ–STIM2 signaling, which in turn increases PDGF-BB-induced Ca2+ elevation. Enhanced expressions of PDGFRs and PLCγ in STIM1 knockout cells induce Ca2+ release from the ER store through PLCγ–IP3 signaling. Moreover, STIM2 replaces STIM1 to act as the major ER Ca2+ sensor in activating SOCE. However, activation of PDGFRs also activate Akt, ERK, and JNK to regulate cellular functions, such as cell migration. These results suggest that alternative switchable pathways can be observed in cells, which act downstream of the growth factors that regulate Ca2+ signaling.

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