The Par-1/MARK family of protein kinases - From polarity to metabolism

The Par-1 protein kinases are conserved from yeast to man and belong to a subfamily of kinases that includes the energy sensor and metabolic regulator, AMPK. Par-1 is regulated by LKB1 and atypical PKC and has been shown in multiple organisms and cell types to be critical for regulation of cellular polarity. Recent studies using knockout mice have revealed several surprising physiological functions for Par-1b/MARK2/EMK1. Our recent study shows that Par-1b regulates metabolic rate, adiposity and insulin sensitivity. This is the first study to implicate these kinases in metabolic functions akin to those previously defined for AMPK. Conversely, another series of recent publications now implicate AMPK in regulation of polarity. Here we discuss the metabolic phenotype seen in Par-1b deficient mice and the synthesis of several findings that link Par-1 and AMPK to a degree that has not been previously appreciated.