Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2006, PMID: 16793766

MAPKAPK-2 is a critical signaling intermediate in NHE3 activation following Na+-glucose cotransport.

Hu, Zhihong; Wang, Yingmin; Graham, W Vallen; Su, Liping; Musch, Mark W; Turner, Jerrold R

Villus enterocyte nutrient absorption occurs via precisely orchestrated interactions among multiple transporters. For example, transport by the apical Na(+)-glucose cotransporter, SGLT1, triggers translocation of NHE3, Na(+)-H(+) antiporter isoform 3, to the plasma membrane. This translocation requires activation of p38 mitogen-activated protein kinase (MAPK), Akt2, and ezrin. Akt2 directly phosphorylates ezrin, but the precise role of p38 MAPK in this process remains to be defined. Sequence analysis suggested that p38 MAPK could not directly phosphorylate Akt2. We hypothesized that MAPKAPK-2 might link p38 MAPK and Akt2 activation. MAPKAPK-2 was phosphorylated after initiation of Na(+)-glucose cotransport with kinetics that paralleled activation of p38 MAPK, Akt2, and ezrin. MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression. Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK-dependent Akt2 activation. Consistent with this, MAP-KAPK-2 could phosphorylate an Akt2-derived peptide in vitro. siRNA-mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK. MAPKAPK-2 knockdown also blocked NHE3 translocation. Thus, MAP-KAPK-2 controls Akt2 phosphorylation. In so doing, MAP-KAPK-2 links p38 MAPK to Akt2, ezrin, and NHE3 activation after SGLT1-mediated transport.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

MAPK ⊣ p38: " MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

ezrin → MAPK: " MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

ezrin → p38: " MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

Akt2 → MAPK: " MAPKAPK-2, Akt2 , and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

Akt2 → p38: " MAPKAPK-2, Akt2 , and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

MAPKAPK-2 → MAPK: " MAPKAPK-2 , Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

MAPKAPK-2 → p38: " MAPKAPK-2 , Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression "

ezrin → Akt2: " Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK dependent Akt2 activation "

p38 → MAPK: " Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK dependent Akt2 activation "

MAPK → Akt2: " Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK dependent Akt2 activation "

MAPKAPK-2 → Akt2: " Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK dependent Akt2 activation "

ezrin ⊣ MAPKAPK-2: " siRNA mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK "

MAPK ⊣ MAPKAPK-2: " siRNA mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK "

Akt2 ⊣ MAPKAPK-2: " siRNA mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK "

Akt2 — MAP-KAPK-2: " Thus, MAP-KAPK-2 controls Akt2 phosphorylation "

Akt2 — MAP-KAPK-2: " Thus, MAP-KAPK-2 controls Akt2 phosphorylation "

Manually curated Databases

  • IRef Innatedb Interaction: AKT2 — MAPKAPK2 (unknown, -)
In total, 1 gene pairs are associated to this article in curated databases