KSR2

Kinase Suppressor of Ras 2 (KSR2) is a scaffold protein that modulates the Ras–mitogen-activated protein kinase (MAPK) signaling pathway. It is encoded by the KSR2 gene in humans and belongs to the KSR family, which also includes KSR1. KSR proteins organize signaling complexes by binding RAF kinases, MEK, and ERK to influence pathway activation and duration.

Biochemical features: KSR2 contains a kinase-like domain that is generally considered catalytically inactive, as well as other regulatory motifs that mediate protein–protein interactions. Its primary role is to bring components of the MAPK cascade into proximity, enabling efficient signal transduction in response to upstream cues.

Expression and physiological roles: KSR2 is expressed in various tissues, with notable enrichment in brain regions and adipose tissue. Through its scaffolding activity, it participates in developmental decisions and cellular differentiation, and in mammals it has been linked to energy homeostasis and feeding behavior.

Genetic and clinical significance: In mouse models, loss of KSR2 disrupts energy balance and leads to obesity and metabolic abnormalities, highlighting a role in metabolism. In humans, rare variants or mutations in KSR2 have been associated with severe obesity and insulin resistance, suggesting a contribution to metabolic disease.

Research status: KSR2 continues to be studied to understand tissue-specific signaling dynamics, interactions with other scaffold proteins, and potential therapeutic implications for metabolic disorders.