NDR (nuclear dbf2-related) kinases, a subclass of AGC kinases, are a highly evolutionarily conserved class of proteins that help regulate proper cell function related to development, growth, and mitotic events.
Function and medical relevance
Like all AGC kinases, the NDR kinase subclass becomes activated when phosphorylated at conserved Ser/Thr residues located within their activation domain. What is specific to the NDR kinases is that they also possess an auto-inhibitory domain that is located in the kinase domain, in addition to an N-terminal regulatory motif known as the SMA domain that binds to MOB proteins. This NDR kinase family can be further divided into two subgroups, the Ndr family and the Wts/Lats family. Humans have four NDR kinases: Ndr1 (or STK38), Ndr2 (or STK38L), Lats1 (large tumor suppressor-1) and Lats2. In higher eukaryotes these kinases have roles in the regulation of many processes, such as tumor suppression, proto-oncogenic activity, apoptosis, centrosome duplication and neuronal differentiation.
In lower eukaryotes, such as the fission yeast Schizosaccharomyces pombe (a model system amenable for the study of cell morphogenesis), the Ndr kinase Orb6 has a role in cell polarity and morphogenesis control in part by the regulation of Cdc42, a small Rho-type GTPase. Specifically, Orb6 kinase spatially restricts Cdc42 activation to be at the polarized tips of a cell, causing the Cdc42-dependent formins, For3 (an F-actin cable polymerization factor), to also be activated at the cell tips, ensuring proper cell growth and polarization. Upon loss of Orb6 kinase function, cells fail to maintain a polarized cell shape and become round.