Neurosci Res 2009,
PMID: 19379779
Chen, Xinyu; Fu, Wen; Tung, Christie E; Ward, Nicole L
Overexpression of angiopoietin (Ang) 1 in the brain results in increased vascularization and altered neuronal dendrite configuration. We hypothesized that Ang1 acts directly on neurons inducing neurite outgrowth. We stimulated PC12 cells with Ang1 and observed outgrowth levels comparable to nerve growth factor (NGF). Western blotting and RT-PCR demonstrated the absence of the Ang1 receptor, Tie2 and the presence of beta1-integrin. Downstream of beta1-integrin, Ang1 stimulation led to a approximately 2.6 fold increase in focal adhesion kinase (FAK) phosphorylation and no change in the activation of mitogen-activated protein kinase (MAPK) nor c-Jun N-terminal kinase (JNK). Conversely, NGF stimulation had no effect on FAK phosphorylation but led to a approximately 3.1 and approximately 2 fold increase in phosphorylation of MAPK and JNK. Ang1, but not NGF-mediated outgrowth was attenuated following functional inhibition of beta1-integrin and FAK, and Wortmannin inhibited neurite outgrowth mediated by both. Our results suggest that Ang1 induces neurite outgrowth in PC12 cells in a Tie2-independent, beta1-integrin-FAK-PI3K-Akt-dependent manner and that NGF and Ang1 mediate neurite outgrowth via two independent signaling mechanisms.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed
Text Mining Data
mitogen activated protein kinase → Ang1: "
Downstream of beta1-integrin,
Ang1 stimulation
led to a approximately 2.6 fold increase in focal adhesion kinase ( FAK ) phosphorylation and no change in the activation of
mitogen activated protein kinase ( MAPK ) nor c-Jun N-terminal kinase (JNK)
"
c-Jun N-terminal kinase (JNK) → Ang1: "
Downstream of beta1-integrin, Ang1 stimulation led to a approximately 2.6 fold increase in focal adhesion kinase ( FAK ) phosphorylation and no change in the activation of mitogen activated protein kinase ( MAPK ) nor c-Jun N-terminal kinase (JNK)
"
MAPK → NGF: "
Conversely, NGF stimulation had no effect on FAK phosphorylation but led to a approximately 3.1 and approximately 2 fold increase in phosphorylation of MAPK and JNK
"
Manually curated Databases
No curated data.