Nair , A. and Chakraborty , S. and Saha , B. (2023) CD40 induces selective routing of Ras isoformsto subcellular compartments. Journal of Cell Communication and Signaling.
Full text not available from this repository. (Request a copy)Abstract
Ras GTPases are central to cellular signaling and oncogenesis. The three loci of the Ras gene encode for four protein isoforms namely Harvey-Ras (H-Ras), Kirsten-Ras (K-Ras 4A and 4B), and Neuroblastoma-Ras (N-Ras) which share ~ 80% sequence similarity and used to be considered functionally redundant. The small molecule inhibitors of Ras lack specificity for the isoforms leading to widespread toxicity in Ras-targeted therapeutics. Ras isoforms’ tissue-specific expression and selective association with carcinogenesis, embryonic development, and infection suggested their non-redundancy. We show that CD40, an antigen-presenting cell (APC)-expressed immune receptor, induces selective relocation of H-Ras, K-Ras, and N-Ras to the Plasma membrane (PM) lipid rafts, mitochondria, endoplasmic reticulum (ER), but not to the Golgi complex (GC). The two palmitoylated Ras isoforms—H-Ras and N-Ras—have a similar pattern of colocalization into the lipid-rich raft microdomain of the PM at early time points when compared to non-palmitoylated K-Ras (4B) with polylysine residues. CD40-induced trafficking of H-Ras and K-Ras to mitochondria and ER was found to be similar but different from that of N-Ras. Trafficking of all the Ras isoforms to the GC was independent of CD40 stimulation. The receptor-driven trafficking and spatial segregation of H-Ras, K-Ras, and N-Ras imply isoform-specific subcellular signaling platforms for the functional non-redundancy of Ras isoforms.
Item Type: | Article |
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Subjects: | Infection and Immunity |
Depositing User: | Mr. Rameshwar Nema |
Date Deposited: | 26 May 2023 09:52 |
Last Modified: | 26 May 2023 09:52 |
URI: | http://nccs.sciencecentral.in/id/eprint/1267 |
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