Regulation of apoptosis by parathyroid hormone-related protein (WP3872)

Homo sapiens

This pathway is based on Figure 8 of "Parathyroid hormone-related protein regulates cell survival pathways via integrin alpha6beta4-mediated activation of phosphatidylinositol 3-kinase/Akt signaling."(See Bibliography). Parathyroid Hormone-related Protein Regulates Cell Survival Pathways via Integrin alpha6beta4-mediated Activation of PI3-K/Akt Signaling Intracrine PTHrP inhibits apoptosis by activating the PI3-K/Akt pathway by increasing levels of integrin A6B4, which signals in harmony with growth factor receptors. The activation of Akt increases the ratio of anti-apoptosis members to pro-apoptosis members in the Bcl-2 Family. The activation of Akt deactivates GSK-3 which leads to higher levels of c-myc, therefore leading to lower levels of apoptosis. Overall, intracrine PTHrP has the effect of increased cell survival on C4-2 cells. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3872 CPTAC Assay Portal]

Authors

AAR&Co , Friederike Ehrhart , Egon Willighagen , Kristina Hanspers , Alex Pico , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

regulatory pathway

Disease Ontology

prostate cancer

Participants

Label Type Compact Identifier Comment
Intracrine PTHrP GeneProduct ensembl:ENSG00000087494
Integrin A6 GeneProduct ensembl:ENSG00000091409
Integrin B4 GeneProduct ensembl:ENSG00000132470
PI3-K GeneProduct ensembl:ENSG00000105851
AKT1 GeneProduct ensembl:ENSG00000142208
BCL2 GeneProduct ensembl:ENSG00000171791 Increases the ratio of anti-apoptosis members to pro-apoptosis members.
GSK3B GeneProduct ensembl:ENSG00000082701
MYC GeneProduct ensembl:ENSG00000136997
BCL2L1 GeneProduct ensembl:ENSG00000171552
BCL2L2 GeneProduct ensembl:ENSG00000129473
BCL2L10 GeneProduct ensembl:ENSG00000137875
BCL2A1 GeneProduct ensembl:ENSG00000140379
BAX GeneProduct ensembl:ENSG00000087088
BAK1 GeneProduct ensembl:ENSG00000030110
BOK GeneProduct ensembl:ENSG00000176720
BID GeneProduct ensembl:ENSG00000015475
BCL2L12 GeneProduct ensembl:ENSG00000126453
BCL2L13 GeneProduct ensembl:ENSG00000099968
BCL2L14 GeneProduct ensembl:ENSG00000121380
BCL2L15 GeneProduct ensembl:ENSG00000188761
GSK3A GeneProduct ensembl:ENSG00000105723
MCL-1 Protein uniprot:Q07820

References

  1. Parathyroid hormone-related protein regulates cell survival pathways via integrin alpha6beta4-mediated activation of phosphatidylinositol 3-kinase/Akt signaling. Bhatia V, Mula RV, Weigel NL, Falzon M. Mol Cancer Res. 2009 Jul;7(7):1119–31. PubMed Europe PMC Scholia