Canonical and noncanonical roles of Par-1/MARK kinases in cell migration.

The partitioning defective gene 1 (Par-1)/microtubule affinity-regulating kinase (MARK) family of serine-threonine kinases have diverse cellular roles. Primary among these roles are the establishment and maintenance of cell polarity and the promotion of microtubule dynamics. Par-1/MARK kinases also regulate a growing number of cellular functions via noncanonical protein targets. Recent studies have demonstrated that Par-1/MARK proteins are required for the migration of multiple cell types. This review outlines the current evidence for regulation of cell migration by Par-1/MARK through both canonical and noncanonical roles. Par-1/MARK canonical control of microtubules during nonneuronal and neuronal migration is described. Next, regulation of cell polarity by Par-1/MARK and its dynamic effect on the movement of migrating cells are discussed. As examples of recent research that have expanded, the roles of the Par-1/MARK in cell migration, noncanonical functions of Par-1/MARK in Wnt signaling and actomyosin dynamics are described. This review also highlights questions and current challenges to further understanding how the versatile Par-1/MARK proteins function in cell migration during development, homeostatic processes, and cancer.