Kinase suppressor of Ras 1 (KSR1)

Kinase suppressor of Ras 1 (KSR1) is a multifunctional protein that acts both as a scaffold and, in some contexts, as an active kinase within the Ras-RAF-MEK-ERK/MAPK signaling pathway[1][2][5]. KSR1 binds to and coordinates the assembly of multiple pathway components (RAF, MEK, ERK), facilitating precise signal transduction involved in cell proliferation, differentiation, survival, and fate determination[5][1]. It was originally described as a positive modulator of Ras signaling in model organisms and is highly evolutionarily conserved in mammals[3]. Numerous studies point to its dual nature: while sometimes referred to as a pseudokinase due to variations in its kinase domain, accumulating evidence shows it possesses catalytic kinase activity under certain conditions[2][5]. KSR1 plays a crucial role in oncogenesis, particularly in tumors with activated Ras or BRAF, by supporting transformation, migration, and survival of cancer cells[1][3][5]. Its loss impairs proliferation, induces cell death and senescence, and suppresses tumorigenic potential in various models. Preclinical strategies to target KSR1 (such as antisense oligonucleotides) are under investigation for potential roles in treating Ras-driven malignancies[3]. KSR1 has also been proposed as a biomarker in breast cancer[6].

Other names

KSR1KSRRSU2kinase suppressor of Ras 1

Antisense inhibition suppresses Ras-mediated oncogenic signaling, leading to tumor regression\nKSR1 inhibitors (hypothetical) would disrupt scaffolding of MAPK signaling components