C. elegans serine-threonine kinase KIN-29 modulates TGFbeta signaling and regulates body size formation.
BACKGROUND
In C. elegans there are two well-defined TGFbeta-like signaling pathways. The Sma/Mab pathway affects body size morphogenesis, male tail development and spicule formation while the Daf pathway regulates entry into and exit out of the dauer state. To identify additional factors that modulate TGFbeta signaling in the Sma/Mab pathway, we have undertaken a genetic screen for small animals and have identified kin-29.


RESULTS
kin-29 encodes a protein with a cytoplasmic serine-threonine kinase and a novel C-terminal domain. The kinase domain is a distantly related member of the EMK (ELKL motif kinase) family, which interacts with microtubules. We show that the serine-threonine kinase domain has in vitro activity. kin-29 mutations result in small animals, but do not affect male tail morphology as do several of the Sma/Mab signal transducers. Adult worms are smaller than the wild-type, but also develop more slowly. Rescue by kin-29 is achieved by expression in neurons or in the hypodermis. Interaction with the dauer pathway is observed in double mutant combinations, which have been seen with Sma/Mab pathway mutants. We show that kin-29 is epistatic to the ligand dbl-1, and lies upstream of the Sma/Mab pathway target gene, lon-1.


CONCLUSIONS
kin-29 is a new modulator of the Sma/Mab pathway. It functions in neurons and in the hypodermis to regulate body size, but does not affect all TGFbeta outputs, such as tail morphogenesis.
Maduzia
Lisa L
LL
Waksman Institute, Department of Molecular Biology and Biochemistry, and Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854-8020, USA. Lisa.Maduzia@umassmed.edu
Roberts
Andrew F
AF
Wang
Huang
H
Lin
Xia
X
Chin
Lena J
LJ
Zimmerman
Cole M
CM
Cohen
Stephen
S
Feng
Xin-Hua
XH
Padgett
Richard W
RW
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000201:enzymology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D040521:Subcutaneous Tissue / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; D009479:Neuropeptides; D016212:Transforming Growth Factor beta; D012313:RNA; C448260:kin-29 protein, C elegans; D017346:Protein Serine-Threonine Kinases