Kinase suppressor of Ras 1 and 2 (KSR1/2)

Kinase Suppressor of Ras (KSR) proteins, specifically KSR1 and KSR2, are critical scaffold proteins that regulate the intensity and duration of the Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway (UniProt Q8IVT5, Q6VAB6). KSR1 is widely expressed and primarily facilitates oncogenic signaling in Ras-driven cancers, where it assembles the Raf-MEK complex to promote downstream ERK activation (PMID: 26766444). KSR2 plays a distinct and pivotal role in the central nervous system, regulating energy expenditure and glucose metabolism; its deficiency is associated with severe obesity (PMID: 24158438). Because KSR proteins are essential for the survival of cells with hyperactivated Ras signaling but are often less critical for normal cell function, they represent high-value targets for precision oncology (PMID: 28847917). Therapeutic strategies include the development of allosteric inhibitors that lock KSR in an inactive conformation or disrupt its interaction with MEK, aiming to overcome resistance to current MAPK-targeted therapies.

Other names

KSR1KSR2Kinase suppressor of Ras 1Kinase suppressor of Ras 2RSU2

Allosteric inhibition of the KSR-MEK complex and disruption of the Raf/MEK/ERK scaffold assembly.