mitogen-activated protein kinase kinase kinase MLT; human cervical cancer suppressor gene 4 protein; HCCS-4; leucine zipper- & sterile alpha motif-containing kinase; MLK-like mitogen-activated protein triple kinase; mixed lineage kinase-related kinase; MLK-related kinase; MRK; sterile alpha motif- & leucine zipper-containing kinase AZK (MLTK, ZAK, HCCS4)
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Function
- stress-activated serine/threonine protein kinase
- regulates the JNK & p38 pathways
- promotes apoptotis
- regulation of S & G2 cell cycle checkpoint via phosphorylation of CHEK2
- isoform 1, but not isoform 2, causes cell shrinkage & disruption of actin stress fibers
- isoform 1, but not isoform 2, phosphorylates histone H3 at Ser-28
- activated by phosphorylation by PKN1
- phosphorylated on Ser-339, Ser-429, Ser-434 & Ser-454
- autophosphorylation on Thr-161 & Ser-165
- interacts with PKN1 & ZNF33A
Structure
- homodimer
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain
- contains 1 SAM (sterile alpha motif) domain
Compartment
- cytoplasm, nucleus
- translocates to the nucleus upon ultraviolet B irradiation
Alternative splicing
named isoforms=3
Expression
- ubiquitously expressed
- isoform 2 is the predominant form in most tissues
- isoform 1 is predominant in liver
Pathology
- isoform 1 may have role in neoplastic transformation