LRRK1

Leucine-rich repeat serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the LRRK1 gene. Formation of LRRK1:EGF-R complexes result in LRRK cellular translocation: LRRK1 traffics together with EGF-R to endosomes upon stimulation of the receptor with EGF. LRRK1 is related to the familial Parkinsonism gene product Park8/LRRK2, and contains a Ras of complex proteins (ROC) GTPase domain and a MAPKKK-like kinase domain. LRRK1 participates in the intercellular trafficking of the epidermal growth factor (EGF) receptor. LRRK1 is activated by the sequential phosphorylation of 2 mitotic kinases, PLK1 and CDK1. Importantly, this PLK1-dependent activation of LRRK1 is required for the regulation of mitotic spindle orientation.LRRK1 regulates spindle orientation in a manner dependent on its kinase activity. Furthermore, the spindle misorientation caused by PLK1 inactivation is rescued by expression of the phospho-mimicking mutant LRRK1(S1790D). LRRK1 regulates spindle orientation downstream of PLK1.