kin-18, a C. elegans protein kinase involved in feeding.
TAO1 and TAO2 are recently described protein kinases whose initial characterization has placed them at the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase kinase (MEKK) level of stress-responsive MAPK pathways. Because their physiological roles have not been identified, we sought to study their C. elegans homolog to learn more about their functions. kin-18 encodes a previously uncharacterized protein in C. elegans whose catalytic domain shares over 60% identity with TAO1 and TAO2. We demonstrate that KIN-18 is a protein of 120 kDa whose promoter is active in the pharynx and intestine of C. elegans. To learn more about TAO/KIN-18 function, we studied how expression of constitutively active forms of TAO1 or KIN-18 would affect the physiology of intact worms. Strains of C. elegans expressing active forms of TAO1 or KIN-18 exhibit altered pharyngeal electrophysiology as measured by electropharyngeogram. These worms grow more slowly and lay fewer eggs, phenotypes that could result from reduced feeding. We have also identified a C. elegans gene that encodes a protein kinase similar to mammalian MAPK/ERK Kinase (MEK) 4 whose promoter is active in the pharynx. It is phosphorylated by TAO1 in vitro and physically interacts with TAO1.
Berman
K S
KS
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA.
Hutchison
M
M
Avery
L
L
Cobb
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D005247:Feeding Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016254:Mutagenesis, Insertional; D009154:Mutation; D010614:Pharynx / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015801:Helminth Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C115483:TAO1 protein kinase; D020930:MAP Kinase Kinase Kinases