Gene interactions and pathways from curated databases and text-mining
J Endocrinol 2002, PMID: 12176662

Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells.

Trümper, A; Trümper, K; Hörsch, D

Glucose-dependent insulinotropic polypeptide (GIP) acts as a glucose-dependent growth factor for beta-cells. Here we show that GIP and glucose also act synergistically as anti-apoptotic factors for beta-cells, using the well-differentiated beta-cell line, INS-1. Mitogenic and anti-apoptotic signaling of GIP were dependent upon pleiotropic activation of protein kinase A (PKA)/cAMP regulatory element binder (CREB), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase)/PKB signaling modules. The signaling modules activated by GIP were dependent on glucose metabolism and calcium influx and were tightly linked by multiple activating and inhibiting cross-talk. These interactions included: (i) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, (ii) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, (iii) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and (iv) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream. Furthermore, we demonstrated inhibition of CREB signaling by Ca(2+)/calmodulin kinase I/IV. These results indicated that GIP acts as a mitogenic and anti-apoptotic factor for beta-cells by pleiotropic activation of tightly linked signaling pathways in beta-cells.

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

Text Mining Data

PKA/CREB ⊣ PKA: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PKA/CREB → MAPK: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PKA/CREB → PKB: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PKA/CREB → PI3-kinase: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

MAPK → PKB: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

MAPK → PI3-kinase: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

MAPK → PKA: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PKB → PI3-kinase: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PKB → PKA: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

PI3-kinase → PKA/CREB: " These interactions included : ( i ) a central role of tyrosine phosphorylation for stimulation of PKA/CREB, MAPK and PI3-kinase/PKB, ( ii ) inhibition of PKA/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, ( iii ) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1/2 or upstream, and ( iv ) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream "

Manually curated Databases

No curated data.