Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2007, PMID: 17209049

AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro.

Bogush, Alexey; Pedrini, Steve; Pelta-Heller, Joshua; Chan, Tung; Yang, Qian; Mao, Zixu; Sluzas, Emily; Gieringer, Tracy; Ehrlich, Michelle E

Mature striatal medium size spiny neurons express the dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa (DARPP-32), but little is known about the mechanisms regulating its levels or the specification of fully differentiated neuronal subtypes. Cell extrinsic molecules that increase DARPP-32 mRNA and/or protein levels include brain-derived neurotrophic factor (BDNF), retinoic acid, and estrogen. DARPP-32 induction by BDNF in vitro requires phosphatidylinositide 3-kinase (PI3K), but inhibition of phosphorylation of protein kinase B/Akt does not entirely abolish expression of DARPP-32. Moreover, the requirement for Akt has not been established. Using pharmacologic inhibitors of PI3K, Akt, and cyclin-dependent kinase 5 (cdk5) and constitutively active and dominant negative PI3K, Akt, cdk5, and p35 viruses in cultured striatal neurons, we measured BDNF-induced levels of DARPP-32 protein and/or mRNA. We demonstrated that both the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction pathways contribute to the induction of DARPP-32 protein levels by BDNF and that the effects are on both the transcriptional and translational levels. It also appears that PI3K is upstream of cdk5/p35, and its activation can lead to an increase in p35 protein levels. These data support the presence of multiple signal transduction pathways mediating expression of DARPP-32 in vitro, including a novel, important pathway via by which PI3K regulates the contribution of cdk5/p35.

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

Text Mining Data

DARPP-32 → CDK5/p35: " AKT and CDK5/p35 mediate brain derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro "

DARPP-32 → AKT: " AKT and CDK5/p35 mediate brain derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro "

DARPP-32 → CDK5/p35: " AKT and CDK5/p35 mediate brain derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro "

phosphatidylinositide 3-kinase (PI3K) → BDNF: " DARPP-32 induction by BDNF in vitro requires phosphatidylinositide 3-kinase (PI3K) , but inhibition of phosphorylation of protein kinase B/Akt does not entirely abolish expression of DARPP-32 "

phosphatidylinositide 3-kinase (PI3K) → DARPP-32: " DARPP-32 induction by BDNF in vitro requires phosphatidylinositide 3-kinase (PI3K) , but inhibition of phosphorylation of protein kinase B/Akt does not entirely abolish expression of DARPP-32 "

DARPP-32 → BDNF: " DARPP-32 induction by BDNF in vitro requires phosphatidylinositide 3-kinase (PI3K), but inhibition of phosphorylation of protein kinase B/Akt does not entirely abolish expression of DARPP-32 "

DARPP-32 → BDNF: " Using pharmacologic inhibitors of PI3K, Akt, and cyclin dependent kinase 5 (cdk5) and constitutively active and dominant negative PI3K, Akt, cdk5, and p35 viruses in cultured striatal neurons, we measured BDNF induced levels of DARPP-32 protein and/or mRNA "

DARPP-32 → BDNF: " We demonstrated that both the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction pathways contribute to the induction of DARPP-32 protein levels by BDNF and that the effects are on both the transcriptional and translational levels "

DARPP-32 → PI3K/Akt/mammalian: " We demonstrated that both the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction pathways contribute to the induction of DARPP-32 protein levels by BDNF and that the effects are on both the transcriptional and translational levels "

DARPP-32 → PI3K/Akt/mammalian target of rapamycin: " We demonstrated that both the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction pathways contribute to the induction of DARPP-32 protein levels by BDNF and that the effects are on both the transcriptional and translational levels "

DARPP-32 → PI3K/Akt/mammalian: " We demonstrated that both the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction pathways contribute to the induction of DARPP-32 protein levels by BDNF and that the effects are on both the transcriptional and translational levels "

Manually curated Databases

No curated data.