Distinct biological roles for the Notch ligands jagged-1 and jagged-2

Kuicheon Choi, Young Ho Ahn, Don L. Gibbons, Hai T. Tran, Chad J. Creighton, Luc Girard, John D. Minna, F. Xiao Feng Qin, Jonathan M. Kurie

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Notch signaling is activated in a subset of non-small cell lung cancer cells because of overexpression of Notch3, but the role of Notch ligands has not been fully defined. On the basis of gene expression profiling of a panel of non-small cell lung cancer cell lines, we found that the predominant Notch ligands were JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping receptor binding specificities, we postulated that they have redundant biological roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were differentially regulated; JAG1 expression was dependent upon epidermal growth factor receptor (EGFR) activation in HCC827 cells, which require EGFR for survival, whereas JAG2 expression was EGFR-independent in these cells. Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes. JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes, including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that JAG1 and JAG2 have distinct biological roles including a previously undiscovered role for JAG2 in regulating the expression of cytokines that can promote antitumor immunity.

Original languageEnglish (US)
Pages (from-to)17766-17774
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number26
DOIs
StatePublished - Jun 26 2009

Fingerprint

Cells
Epidermal Growth Factor Receptor
Ligands
Interleukin-1
Cytokines
Non-Small Cell Lung Carcinoma
Interleukin-1 Receptors
Gene expression
Genes
Chemical activation
Gene Expression Profiling
Apoptosis
Coculture Techniques
Jagged-1 Protein
Monocytes
Immunity
Inflammation
Cell Line
Survival
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Choi, K., Ahn, Y. H., Gibbons, D. L., Tran, H. T., Creighton, C. J., Girard, L., ... Kurie, J. M. (2009). Distinct biological roles for the Notch ligands jagged-1 and jagged-2. Journal of Biological Chemistry, 284(26), 17766-17774. https://doi.org/10.1074/jbc.M109.003111

Distinct biological roles for the Notch ligands jagged-1 and jagged-2. / Choi, Kuicheon; Ahn, Young Ho; Gibbons, Don L.; Tran, Hai T.; Creighton, Chad J.; Girard, Luc; Minna, John D.; Qin, F. Xiao Feng; Kurie, Jonathan M.

In: Journal of Biological Chemistry, Vol. 284, No. 26, 26.06.2009, p. 17766-17774.

Research output: Contribution to journalArticle

Choi, K, Ahn, YH, Gibbons, DL, Tran, HT, Creighton, CJ, Girard, L, Minna, JD, Qin, FXF & Kurie, JM 2009, 'Distinct biological roles for the Notch ligands jagged-1 and jagged-2', Journal of Biological Chemistry, vol. 284, no. 26, pp. 17766-17774. https://doi.org/10.1074/jbc.M109.003111
Choi, Kuicheon ; Ahn, Young Ho ; Gibbons, Don L. ; Tran, Hai T. ; Creighton, Chad J. ; Girard, Luc ; Minna, John D. ; Qin, F. Xiao Feng ; Kurie, Jonathan M. / Distinct biological roles for the Notch ligands jagged-1 and jagged-2. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 26. pp. 17766-17774.
@article{c505b988768446d78fa54dadd26051b4,
title = "Distinct biological roles for the Notch ligands jagged-1 and jagged-2",
abstract = "Notch signaling is activated in a subset of non-small cell lung cancer cells because of overexpression of Notch3, but the role of Notch ligands has not been fully defined. On the basis of gene expression profiling of a panel of non-small cell lung cancer cell lines, we found that the predominant Notch ligands were JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping receptor binding specificities, we postulated that they have redundant biological roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were differentially regulated; JAG1 expression was dependent upon epidermal growth factor receptor (EGFR) activation in HCC827 cells, which require EGFR for survival, whereas JAG2 expression was EGFR-independent in these cells. Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes. JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes, including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that JAG1 and JAG2 have distinct biological roles including a previously undiscovered role for JAG2 in regulating the expression of cytokines that can promote antitumor immunity.",
author = "Kuicheon Choi and Ahn, {Young Ho} and Gibbons, {Don L.} and Tran, {Hai T.} and Creighton, {Chad J.} and Luc Girard and Minna, {John D.} and Qin, {F. Xiao Feng} and Kurie, {Jonathan M.}",
year = "2009",
month = "6",
day = "26",
doi = "10.1074/jbc.M109.003111",
language = "English (US)",
volume = "284",
pages = "17766--17774",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - Distinct biological roles for the Notch ligands jagged-1 and jagged-2

AU - Choi, Kuicheon

AU - Ahn, Young Ho

AU - Gibbons, Don L.

AU - Tran, Hai T.

AU - Creighton, Chad J.

AU - Girard, Luc

AU - Minna, John D.

AU - Qin, F. Xiao Feng

AU - Kurie, Jonathan M.

PY - 2009/6/26

Y1 - 2009/6/26

N2 - Notch signaling is activated in a subset of non-small cell lung cancer cells because of overexpression of Notch3, but the role of Notch ligands has not been fully defined. On the basis of gene expression profiling of a panel of non-small cell lung cancer cell lines, we found that the predominant Notch ligands were JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping receptor binding specificities, we postulated that they have redundant biological roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were differentially regulated; JAG1 expression was dependent upon epidermal growth factor receptor (EGFR) activation in HCC827 cells, which require EGFR for survival, whereas JAG2 expression was EGFR-independent in these cells. Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes. JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes, including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that JAG1 and JAG2 have distinct biological roles including a previously undiscovered role for JAG2 in regulating the expression of cytokines that can promote antitumor immunity.

AB - Notch signaling is activated in a subset of non-small cell lung cancer cells because of overexpression of Notch3, but the role of Notch ligands has not been fully defined. On the basis of gene expression profiling of a panel of non-small cell lung cancer cell lines, we found that the predominant Notch ligands were JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping receptor binding specificities, we postulated that they have redundant biological roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were differentially regulated; JAG1 expression was dependent upon epidermal growth factor receptor (EGFR) activation in HCC827 cells, which require EGFR for survival, whereas JAG2 expression was EGFR-independent in these cells. Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes. JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes, including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that JAG1 and JAG2 have distinct biological roles including a previously undiscovered role for JAG2 in regulating the expression of cytokines that can promote antitumor immunity.

UR - http://www.scopus.com/inward/record.url?scp=67650519059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650519059&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.003111

DO - 10.1074/jbc.M109.003111

M3 - Article

VL - 284

SP - 17766

EP - 17774

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -