NDR Kinase
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NDR (
nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...
dbf2-related)
kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
s, are an ancient and highly conserved subclass of AGC protein kinases that control diverse processes related to cell morphogenesis, proliferation, and
mitotic Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the t ...
events.


Function and medical relevance

Like most AGC kinases, the NDR kinase subclass is activated by phosphorylation of a conserved serine or threonine in an activation region C-terminal to the kinase catalytic domain. The NDR kinases are distinguished by an apparently functionally essential binding of MOB co-activator proteins that are also widely present in eukaryotes. Most NDR kinase catalytic domains also contain an extended insert region that may function as an auto-inhibitory element. The 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 animals these kinases have reported roles in the regulation of diverse processes, including cell proliferation control, activity of proto-oncogenic proteins, apoptosis, centrosome duplication, and organization of neuronal dendrites. In unicellular
eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s, Ndr kinases play important roles in the control of the cell cycle and morphogenesis. In the fission yeast ''Schizosaccharomyces pombe'', an organism 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 small
Rho Rho (; uppercase Ρ, lowercase ρ or ; or ) is the seventeenth letter of the Greek alphabet. In the system of Greek numerals it has a value of 100. It is derived from Phoenician alphabet, Phoenician letter resh . Its uppercase form uses the same ...
-type
GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
Cdc42 Cell division control protein 42 homolog (Cdc42 or CDC42) is a protein that in humans is encoded by the ''CDC42'' gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in ''S. cerevisiae'' (yeast) as a mediator of ...
. Specifically, Orb6 kinase spatially restricts Cdc42 activation to be at the polarized tips of a cell, causing the Cdc42-dependent
formin Formins (formin homology proteins) are a group of proteins that are involved in the polymerization of actin and associate with the fast-growing end (barbed end) of actin filaments. Most formins are Rho-GTPase effector proteins. Formins re ...
s, For3 (an F-
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
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.


References

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