Oncogenic KRas mobility in the membrane and signaling response

Ruth Nussinov*, Chung Jung Tsai, Hyunbum Jang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Ras signaling initiates at the plasma membrane. Thus, Ras behavior at the membrane and how it relates to its interactions with Raf and PI3Kα, are of immense interest. Here we review factors influencing Ras lateral diffusion. We then ask whether oncogenic Ras diffusion speed in the membrane is important for signaling response times and whether it affects ubiquitously all pathways. We suggest that if Ras expression is sufficiently high to dimerize (or form nanoclusters), signaling response of those pathways where dimers (or nanoclusters) are involved corresponds to the speed with which Ras molecules travel in the membrane. On average, the faster the rate at which Ras travels to dimerize, the shorter the time to MAPK signaling; but not PI3Kα. However, we argue that KRas speed may not play an important functional role because changes in mobility at this scale are unlikely to be significant. In line with this, despite the anchors’ variability, lateral diffusion speeds of KRas and HRas are similar, as is that of Lck kinase; however, even though with similar anchor, Cdc42 mobility presents a different pattern, commensurate with its role in the positioning of the apical domain, suggesting that mobility evolved for function.

Original languageEnglish
Pages (from-to)109-113
Number of pages5
JournalSeminars in Cancer Biology
Volume54
DOIs
StatePublished - Feb 2019

Funding

FundersFunder number
National Institutes of HealthHHSN261200800001E
U.S. Department of Health and Human Services
National Cancer InstituteZIABC010440
Frederick National Laboratory for Cancer Research
Government of South Australia

    Keywords

    • Cdc42
    • HRAS
    • K-Ras
    • K-Ras4A
    • K-Ras4B
    • KRAS4A
    • KRAS4B
    • Lck kinase
    • NRAS

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