Amplification of B cell receptor–Erk signaling by Rasgrf-1 overexpression in chronic lymphocytic leukemia
Copyright policy )Amplification of B cell receptor–Erk signaling by Rasgrf-1 overexpression in chronic lymphocytic leukemia
Rasgrf-1 is a guanine exchange factor (GEF) that catalyzes the exchange of GDP for GTP. In a RNA microarray analysis of chronic lymphocytic leukemia (CLL) specimens (n = 5), this gene was found to be overexpressed in CLL as compared to normal peripheral blood mononuclear cell (PBMC) CD19 + B cells (n = 3). CLL specimens (n = 29) expressed Rasgrf-1 RNA at levels 5-300-fold higher as compared to normal B cells. CLL specimens expressed a 75 kDa isoform that was smaller than the expected full-length protein (140 kDa) and the truncated variant had higher GEF activity. Knockdown of Rasgrf-1 in CLL specimens inhibited active GTP-bound Ras and the Ras/Erk/mitogen-activated protein kinase (MAPK) pathway. Rasgrf-1 was phosphorylated and activated by B cell receptor (BCR) signaling that increased its GEF function, and this phosphorylation was blocked by Src and Bruton's tyrosine kinase (BTK) inhibitors. Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens.
- University of California, Los Angeles United States
MAP Kinase Signaling System, ras-GRF1, Gene Expression Profiling, Gene Expression, Receptors, Antigen, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Models, Biological, Gene Knockdown Techniques, ras Proteins, Humans, RNA, Messenger, Phosphorylation, Neoplasm Staging
MAP Kinase Signaling System, ras-GRF1, Gene Expression Profiling, Gene Expression, Receptors, Antigen, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Models, Biological, Gene Knockdown Techniques, ras Proteins, Humans, RNA, Messenger, Phosphorylation, Neoplasm Staging
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).7 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!