Mechanism of activation of NDR protein kinase by the HMOB1 protein

Serine/threonine kinases of the nuclear Dbf2-related (NDR) family are highly
conserved throughout the eukaryotic world. Members of this kinase family are
implicated in various aspects of the regulation of cell division and cell morphology. It
has been shown that the function of several NDR kinases is dependent on proteins of
the Mob (MPS one binder) family. MOB proteins are highly conserved throughout the
eukaryotic world as well, which indicates the existence of a novel conserved signalling
pathway.
The current work focuses on the mechanism of activation of human NDR kinase by
the human MOB1 protein. hMOB1 directly activates NDR by binding to the Nterminal
domain of NDR, thereby hMOB1 acts as a kinase activating subunit of NDR
kinase. The binding induces the release of an autoinhibition caused by an
autoinhibitory sequence (AIS) and leads to increased phosphorylation of NDR kinase
on the two important regulatory phosphorylation sites Ser-281 and Thr-444.