View source for Kinase Subfamily LZK

__NOTOC__
[[kinase classification|Kinase Classification]]: [[Kinase_Group_TKL|Group TKL]]: [[Kinase_Family_MLK|Family MLK]]: : [[Kinase_Subfamily_LZK|Subfamily LZK]]


====Evolution====
LZK is found throughout the holozoa. The two vertebrate members are LZK (MAP3K13) and DLK (MAP3K12).

====Domain Structure====
Most animal LZKs have a kinase domain in the middle, flanked by unannotated regions. Human DLK ("'''D'''ual '''L'''eucine Zipper '''K'''inase")was reported to have two degenerate leucine zipper regions just C-terminal to the kinase domain <cite>Holzman</cite>. These are variably conserved in LZK and in invertebrate homologs. The DLK leucine zippers are involved in homodimerization <cite>Nihalani</cite>.

Kelch domains are seen in some sponge members, and PB1 domains in plants. A C-terminal semi-conserved region contains an identical hexapeptide (SDGLSD) in worm and human LZK and in worm is required for Ca modulation of function <cite>Yan</cite>

====Functions====

Human DLK is largely brain specific, particularly in the cerebellum, while LZK is expressed throughout the body, and at a higher level in the brain.

C. elegans DLK-1 is involved in synaptic development <cite>Kurup</cite> and axon regeneration <cite>Chen, Hammarlund</cite> through modulation of microtubule activity <cite>Kurup, Ghosh-Roy</cite>. Mouse DLK is also implicated in axonal regeneration <cite>Itoh</cite>. A pathway including DLK-1, MKK-4 (a [[Kinase_Subfamily_MEK4|MEK4]] MAPKK) and PMK-3 ([[Kinase_Subfamily_p38|p38]] MAPK), mak-2 ([[Kinase_Family_MAPKAPK|MAPKAPK]] kinase) as well as the ubiquitin ligase RPM-1 is involved in nematode presynaptic development <cite>Nakata</cite>.

C. elegans DLK-1 has two opposing splice isoforms, and a Ca-mediated activation switches from heteromeric to active homomeric complexes.
<cite>Yan</cite>


==== References ====
<biblio>
#Chen pmid=21943602
#Ghosh-Roy pmid=23000142
#Hammarlund pmid=19164707
#Holzman pmid=7983011
#Itoh pmid=19358824
#Kurup pmid=26051896
#Nakata pmid=15707898
#Nihalani pmid=10702297
#Yan pmid=23141066
</biblio>