Gene interactions and pathways from curated databases and text-mining
Am J Physiol Cell Physiol 2005, PMID: 15728708

LPA2 receptor mediates mitogenic signals in human colon cancer cells.

Yun, C Chris; Sun, Hong; Wang, Dongsheng; Rusovici, Raluca; Castleberry, Amanda; Hall, Randy A; Shim, Hyunsuk

Lysophosphatidic acid (LPA) is a mediator of multiple cellular responses. LPA mediates its effects predominantly through the G protein-coupled receptors LPA1, LPA2, and LPA3. In the present work, we studied LPA2-mediated signaling using human colon cancer cell lines, which predominantly express LPA2. LPA2 activated Akt and Erk1/2 in response to LPA. LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122. LPA also induced interleukin-8 (IL-8) synthesis in the colon cancer cells by primarily activating LPA2 receptor. We also found that LPA2 interacts with Na+/H+ exchanger regulatory factor 2 (NHERF2). Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2-mediated signaling. We found that expression of LPA2 was elevated, whereas expression of LPA1 downregulated in several types of cancers, including ovarian and colon cancer. We conclude that LPA2 is the major LPA receptor in colon cancer cells and cellular signals by LPA2 are largely mediated through its ability to interact with NHERF2.

Diseases/Pathways annotated by Medline MESH: Colonic Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Akt → LPA2: " LPA2 activated Akt and Erk1/2 in response to LPA "

Erk1/2 → LPA2: " LPA2 activated Akt and Erk1/2 in response to LPA "

Erk1/2 → LPA: " LPA2 activated Akt and Erk1/2 in response to LPA "

LPA ⊣ pertussis toxin ( PTX ): " LPA mediated Akt activation was inhibited by pertussis toxin ( PTX ) , whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122 "

interleukin-8 (IL-8) → LPA: " LPA also induced interleukin-8 (IL-8) synthesis in the colon cancer cells by primarily activating LPA2 receptor "

Akt → NHERF2: " Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2 mediated signaling "

Erk1/2 → NHERF2: " Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2 mediated signaling "

Erk1/2 → NHERF2: " Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2 mediated signaling "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: LPAR2 (increases, Activity)
    Evidence: Lysophosphatidic acid (LPA) is a mediator of multiple cellular responses. LPA mediates its effects predominantly through the G protein-coupled receptors LPA1, LPA2, and LPA3.
  • OpenBEL Selventa BEL large corpus: AKT1 → LPAR2 (increases, LPAR2 Activity, AKT1 Activity)
    Evidence: In the present work, we studied LPA2-mediated signaling using human colon cancer cell lines, which predominantly express LPA2. LPA2 activated Akt and Erk1/2 in response to LPA.
  • OpenBEL Selventa BEL large corpus: CXCL8 → LPAR2 (increases, CXCL8 Activity)
    Evidence: LPA also induced interleukin-8 (IL-8) synthesis in the colon cancer cells by primarily activating LPA2 receptor.
  • OpenBEL Selventa BEL large corpus: MAPK1 → LPAR2 (increases, LPAR2 Activity, MAPK1 Activity)
    Evidence: In the present work, we studied LPA2-mediated signaling using human colon cancer cell lines, which predominantly express LPA2. LPA2 activated Akt and Erk1/2 in response to LPA.
  • OpenBEL Selventa BEL large corpus: MAPK1 → PLCB1 (increases, PLCB1 Activity, MAPK1 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • OpenBEL Selventa BEL large corpus: MAPK3 → PLCB1 (increases, PLCB1 Activity, MAPK3 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • OpenBEL Selventa BEL large corpus: MAPK1 → PLCB2 (increases, PLCB2 Activity, MAPK1 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • OpenBEL Selventa BEL large corpus: MAPK3 → PLCB3 (increases, PLCB3 Activity, MAPK3 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • OpenBEL Selventa BEL large corpus: MAPK1 → PLCB4 (increases, PLCB4 Activity, MAPK1 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • OpenBEL Selventa BEL large corpus: MAPK3 → PLCB4 (increases, PLCB4 Activity, MAPK3 Activity)
    Evidence: LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cbeta, U-73122.
  • NCI Pathway Database LPA receptor mediated events: LPA/LPA2/NHERF2 complex (LPAR2-SLC9A3R2) → NHERF2 (SLC9A3R2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database LPA receptor mediated events: LPA/LPA2/NHERF2 complex (LPAR2-SLC9A3R2) → LPA/LPA2 complex (LPAR2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database LPA receptor mediated events: NHERF2 (SLC9A3R2) → LPA/LPA2 complex (LPAR2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database LPA receptor mediated events: NF kappa B1 p50/RelA complex (NFKB1-RELA) → IL8 (CXCL8) (transcription, activates)
    Evidence: mutant phenotype, assay, reporter gene
In total, 6 gene pairs are associated to this article in curated databases