Apoptosis regulation by parathyroid hormone-related protein (WP3872)

Homo sapiens

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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). 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 CPTAC Assay Portal

Authors

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

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

regulatory pathway

Disease Ontology

prostate cancer

Participants
Query Drugst.One

Label Type Compact URI Comment
GSK3A GeneProduct ensembl:ENSG00000105723
AKT1 GeneProduct hgnc.symbol:AKT1
BCL2L10 GeneProduct ensembl:ENSG00000137875
ITGA6 GeneProduct ensembl:ENSG00000091409 'Integrin A6' originally
BOK GeneProduct ensembl:ENSG00000176720
BCL2L12 GeneProduct ensembl:ENSG00000126453
BCL2A1 GeneProduct ensembl:ENSG00000140379
BCL2L15 GeneProduct ensembl:ENSG00000188761
ITGB4 GeneProduct ensembl:ENSG00000132470 'Integrin B4' originally
GSK3B GeneProduct ensembl:ENSG00000082701
MYC GeneProduct ensembl:ENSG00000136997
PTHLH GeneProduct ensembl:ENSG00000087494 'Intracrine PTHrP' originally
BID GeneProduct ensembl:ENSG00000015475
BCL2L1 GeneProduct ensembl:ENSG00000171552
PI3-K GeneProduct ensembl:ENSG00000105851
BCL2L2 GeneProduct ensembl:ENSG00000129473
BAK1 GeneProduct ensembl:ENSG00000030110
BCL2L14 GeneProduct ensembl:ENSG00000121380
BCL2 GeneProduct ensembl:ENSG00000171791 Increases the ratio of anti-apoptosis members to pro-apoptosis members.
BAX GeneProduct ensembl:ENSG00000087088
BCL2L13 GeneProduct ensembl:ENSG00000099968
AKT2 GeneProduct hgnc.symbol:AKT2
AKT3 GeneProduct hgnc.symbol:AKT3
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