UCSC Genome Browser Gene Interaction Graph

JavaScript is disabled in your web browser

You must have JavaScript enabled in your web browser to use the Genome Browser

Gene interactions and pathways from curated databases and text-mining

J Cell Sci 2008, PMID: 18946023

p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta.

Bikkavilli, Rama Kamesh; Feigin, Michael E; Malbon, Craig C

The Wnt-beta-catenin canonical signaling pathway is crucial for normal embryonic development, and aberrant expression of components of this pathway results in oncogenesis. Upon scanning for the mitogen-activated protein kinase (MAPK) pathways that might intersect with the canonical Wnt-beta-catenin signaling pathway in response to Wnt3a, we observed a strong activation of p38 MAPK in mouse F9 teratocarcinoma cells. Wnt3a-induced p38 MAPK activation was sensitive to siRNAs against Galpha(q) or Galpha(s), but not against either Galpha(o) or Galpha(11). Activation of p38 MAPK is critical for canonical Wnt-beta-catenin signaling. Chemical inhibitors of p38 MAPK (SB203580 or SB239063) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a-induced accumulation of beta-catenin, Lef/Tcf-sensitive gene activation, and primitive endoderm formation. Furthermore, epistasis experiments pinpoint p38 MAPK as operating downstream of Dishevelleds. We also demonstrate that chemical inhibition of p38 MAPK restores Wnt3a-attenuated GSK3beta kinase activity. We demonstrate the involvement of G-proteins and Dishevelleds in Wnt3a-induced p38 MAPK activation, highlighting a critical role for p38 MAPK in canonical Wnt-beta-catenin signaling.

Document information provided by NCBI PubMed

Text Mining Data

Wnt-beta-catenin → p38: " p38 mitogen activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta "

p38 → Wnt3a: " Wnt3a induced p38 MAPK activation was sensitive to siRNAs against Galpha ( q ) or Galpha ( s ), but not against either Galpha ( o ) or Galpha(11) "

MAPK → Wnt3a: " Wnt3a induced p38 MAPK activation was sensitive to siRNAs against Galpha ( q ) or Galpha ( s ), but not against either Galpha ( o ) or Galpha(11) "

Wnt-beta-catenin → MAPK: " Activation of p38 MAPK is critical for canonical Wnt-beta-catenin signaling "

Lef/Tcf-sensitive → Wnt3a: " Chemical inhibitors of p38 MAPK ( SB203580 or SB239063 ) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a induced accumulation of beta-catenin, Lef/Tcf-sensitive gene activation, and primitive endoderm formation "

Lef/Tcf-sensitive → MAPK: " Chemical inhibitors of p38 MAPK ( SB203580 or SB239063 ) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a induced accumulation of beta-catenin, Lef/Tcf-sensitive gene activation, and primitive endoderm formation "

beta-catenin → Wnt3a: " Chemical inhibitors of p38 MAPK ( SB203580 or SB239063 ) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a induced accumulation of beta-catenin , Lef/Tcf-sensitive gene activation, and primitive endoderm formation "

beta-catenin → MAPK: " Chemical inhibitors of p38 MAPK ( SB203580 or SB239063 ) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a induced accumulation of beta-catenin , Lef/Tcf-sensitive gene activation, and primitive endoderm formation "

GSK3beta ⊣ MAPK: " We also demonstrate that chemical inhibition of p38 MAPK restores Wnt3a attenuated GSK3beta kinase activity "

MAPK → Wnt3a: " We demonstrate the involvement of G-proteins and Dishevelleds in Wnt3a induced p38 MAPK activation, highlighting a critical role for p38 MAPK in canonical Wnt-beta-catenin signaling "

p38 → Wnt3a: " We demonstrate the involvement of G-proteins and Dishevelleds in Wnt3a induced p38 MAPK activation , highlighting a critical role for p38 MAPK in canonical Wnt-beta-catenin signaling "

Manually curated Databases

No curated data.