title: Cloning and characterization of microbial activated Aedes aegypti MEK4 (AaMEK4): influences of noncatalytic domains on enzymatic activity.
abstract: Protein kinases are known to be involved in a number of signal transduction cascades. Both the stress-activated Jun N-terminal kinase (JNK) and mitogen-activated protein kinase (MAPK) p38 pathways have been shown to correlate with the insect immune response to microbial infection. MAP kinase kinase 4 (MEK4) is an upstream kinase of JNK and p38 kinase. The cDNA of AaMEK4 was cloned and characterized. AaMEK4 was activated by microbial lysates of Gram-positive, Gram-negative bacteria and yeast. The conserved lysine (K112 ) and the putative phosphorylation sites (S238 and T242 ) were shown to be important for kinase activity by site-directed mutagenesis. A common MAPK docking site (MAPK_dsA) was found and in addition, a new nearby docking site, MAPK_dsB, was identified in the N-terminal noncatalytic domain of AaMEK4. MAPK_dsB was shown to be a unique element in the MEK4 family. In this study, both MAPK_dsA and _dsB were demonstrated to be important to AaMEK4 enzymatic activity for the downstream protein kinase, Aap38.
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: R C-C
authors.initials: RC
authors.lastname: Wu
authors.forename: W-L
authors.initials: WL
authors.lastname: Cho
mesh_terms: D000330:Aedes / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000201:enzymology; D048670:MAP Kinase Kinase 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010063:Ovum / Q000201:enzymology; D010802:Phylogeny; D011679:Pupa / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D019476:Insect Proteins; D048670:MAP Kinase Kinase 4
keywords: Aedes aegypti; MAPK docking site; innate immunity; protein kinase; signal transduction