Inositol trisphosphate mediates a RAS-independent response to LET-23 receptor tyrosine kinase activation in C. elegans.
Activity of LET-23, the C. elegans homolog of the epidermal growth factor receptor, is required in multiple tissues. RAS activation is necessary and sufficient for certain LET-23 functions. We show that an inositol trisphosphate receptor can act as a RAS-independent, tissue-specific positive effector of LET-23. Moreover, an inositol trisphosphate kinase negatively regulates this transduction pathway. Signals transduced by LET-23 control ovulation through changes in spermathecal dilation, possibly dependent upon calcium release regulated by both IP3 and IP4. Our results demonstrate that one mechanism by which receptor tyrosine kinases can evoke tissue-specific responses is through activation of distinct signal transduction cascades in different tissues.
Clandinin
T R
TR
Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena 91125, USA.
DeModena
J A
JA
Sternberg
P W
PW
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics; D012734:Disorders of Sex Development; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015801:Helminth Proteins / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010060:Ovulation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D015801:Helminth Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C085873:let-23 protein, C elegans; D018631:ras Proteins; D002118:Calcium