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. (C) 2001 Elsevier Science B.V. All rights reserved.