Gene interactions and pathways from curated databases and text-mining
J Cell Physiol 2013, PMID: 23018889

Involvement of Akt2/protein kinase B β (PKBβ) in the 8-Cl-cAMP-induced cancer cell growth inhibition.

Choi, Ki Young; Ahn, Young Ho; Ahn, Hae Won; Cho, Young Jun; Hong, Seung Hwan

8-chloro-cyclic AMP (8-Cl-cAMP), which induces differentiation, growth inhibition, and apoptosis in various cancer cells, has been investigated as a putative anti-cancer drug. However, the exact mechanism of 8-Cl-cAMP functioning in cancer cells is not fully understood. Akt/protein kinase B (PKB) genes (Akt1, Akt2, and Akt3) encode enzymes belonging to the serine/threonine-specific protein kinase family. It has been suggested that Akt/PKB enhances cell survival by inhibiting apoptosis. Recently, we showed that 8-Cl-cAMP and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibited cancer cell growth through the activation of AMPK and p38 MAPK. Therefore, we anticipated that the phosphorylation of Akt/PKB would be decreased upon treatment with 8-Cl-cAMP. However, treatment with 8-Cl-cAMP and AICAR induced the phosphorylation of Akt/PKB, which was inhibited by ABT702 (an adenosine kinase inhibitor) and NBTI (an adenosine transporter inhibitor). Furthermore, whereas Compound C (an AMPK inhibitor), AMPK-DN (AMPK-dominant negative) mutant, and SB203580 (a p38 MAPK inhibitor) did not block the 8-Cl-cAMP-induced phosphorylation of Akt/PKB, TCN (an Akt1/2/3 specific inhibitor) and an Akt2/PKBβ-targeted siRNA inhibited the 8-Cl-cAMP- and AICAR-mediated phosphorylation of AMPK and p38 MAPK. TCN also reversed the growth inhibition mediated by 8-Cl-cAMP and AICAR. Moreover, an Akt1/PKBα-targeted siRNA did not reduce the phosphorylation of AMPK and p38 MAPK after treatment with 8-Cl-cAMP. These results suggest that Akt2/PKBβ activation promotes the phosphorylation of AMPK and p38 MAPK during the 8-Cl-cAMP- and AICAR-induced growth inhibition.

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

Text Mining Data

MAPK ⊣ TCN: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB, TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Akt/PKB ⊣ AMPK-DN: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB , TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Akt/PKB ⊣ AMPK-DN: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB , TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

AMPK ⊣ TCN: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB, TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Akt/PKB → p38: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB , TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Akt/PKB → MAPK: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB , TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Akt/PKB → MAPK: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB , TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

AMPK → p38: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB, TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

AMPK → MAPK: " Furthermore, whereas Compound C ( an AMPK inhibitor ), AMPK-DN ( AMPK-dominant negative ) mutant, and SB203580 ( a p38 MAPK inhibitor ) did not block the 8-Cl-cAMP induced phosphorylation of Akt/PKB, TCN ( an Akt1/2/3 specific inhibitor ) and an Akt2/PKBß targeted siRNA inhibited the 8-Cl-cAMP- and AICAR mediated phosphorylation of AMPK and p38 MAPK "

Manually curated Databases

No curated data.