CAENORHABDITIS-ELEGANS LET-502 IS RELATED TO RHO-BINDING KINASES AND HUMAN MYOTONIC-DYSTROPHY KINASE AND INTERACTS GENETICALLY WITH A HOMOLOG OF THE REGULATORY SUBUNIT OF SMOOTH-MUSCLE MYOSIN PHOSPHATASE TO AFFECT CELL-SHAPE

We have identified two genes associated with the hypodermal cell shape changes that occur during elongation of the Caenorhabditis elegans em bryo. The first gene, called let-502, encodes a protein with high simi larity to Rho-binding Ser/Thr kinases and to human myotonic dystrophy kinase (DM-kinase). Strong mutations in let-502 block embryonic elonga tion, and let-502 reporter constructs are expressed in hypodermal cell s at the elongation stage of development. The second gene, mel-11, was identified by mutations that act as extragenic suppressors of let-502 . mel-11 encodes a protein similar to the 110- to 133-kD regulatory su bunits of vertebrate smooth muscle myosin-associated phosphatase (PP-1 M). We suggest that the LET-502 kinase and the MEL-11 phosphatase subu nit act in a pathway linking a signal generated by the small GTP-bindi ng protein Rho to a myosin-based hypodermal contractile system that dr ives embryonic elongation. LET-502 may directly regulate the activity of the MEL-11 containing phosphatase complex and the similarity betwee n LET-502 and DM-kinase suggests a similar function for DM-kinase.