Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cAMP-dependent protein kinase A (PKA) is a serine/threonine kinase involved in many fundamental cellular processes, including migration and proliferation. Recently, we found that the Src family kinase Fyn phosphorylates the catalytic subunit of PKA (PKA-C) at Y69, thereby increasing PKA kinase activity. We also showed that Fyn induced the phosphorylation of cellular proteins within the PKA preferred target motif. This led to the hypothesis that Fyn could affect proteins in complex with PKA. To test this, we employed a quantitative mass spectrometry approach to identify Fyn-dependent binding partners in complex with PKA-C. We found Fyn enhanced the binding of PKA-C to several cytoskeletal regulators that localize to the centrosome and Golgi apparatus. Three of these Fyn-induced PKA interactors, AKAP9, PDE4DIP, and CDK5RAP2, were validated biochemically and were shown to exist in complex with Fyn and PKA in a glioblastoma cell line. Intriguingly, the complexes formed between PKA-C and these known AKAPs were dependent upon Fyn catalytic activity and expression levels. In addition, we identified Fyn-regulated phosphorylation sites on proteins in complex with PKA-C. We also identified and biochemically validated a novel PKA-C interactor, LARP4, which complexed with PKA in the absence of Fyn. These results demonstrate the ability of Fyn to influence the docking of PKA to specific cellular scaffolds and suggest that Fyn may affect the downstream substrates targeted by PKA.
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PMID:Fyn Regulates Binding Partners of Cyclic-AMP Dependent Protein Kinase A. 3027 58

Lipocalin 2 (LCN2) is a member of the lipocalin family. Elevated expression of LCN2 has been observed in many human tumors, suggesting it might be a potential biomarker and/or therapeutic target in malignancies. In this study, we aimed to explore LCN2 interacting proteins through bioinformatics, as well as their biological functions. Protein-protein interaction networks (PPIN) were constructed using LCN2 and its interacting proteins as the core node. These PPINs were scale free biological networks in which LCN2 and its interacting proteins could connect or cross-talk with at least one partner protein. Both functional and KEGG pathway enrichment analyses identified the known and potential biological functions of the PPIN, such as cell migration and cancer-related pathways. Expression levels of the PPIN proteins, as well as their expression correlations, in five types of brain tumor, were analyzed and integrated into the PPIN to illustrate a dynamic change. A significant correlation was found between the survival time of glioblastoma patients and the expression level of 10 genes (LCN2, MMP9, MMP2, PDE4DIP, L2HGDH, HNRNPA1, DDX31, LOXL2, FAM60A and RNF25). Taken together, our results suggest that LCN2 and its interacting proteins are mostly differentially expressed and have a distinguishing co-expression pattern. They might promote proliferation and migration via cell migration signaling and cancer-related pathways. LCN2 and its interacting proteins might be potential biomarkers in glioblastoma.
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PMID:LCN2-interacting proteins and their expression patterns in brain tumors. 3123 12