Tr. Clandinin et al., INOSITOL TRISPHOSPHATE MEDIATES A RAS-INDEPENDENT RESPONSE TO LET-23 RECEPTOR TYROSINE KINASE ACTIVATION IN C-ELEGANS, Cell, 92(4), 1998, pp. 523-533
Activity of LET-23, the C. elegans homolog of the epidermal growth fac
tor receptor, is required in multiple tissues. RAS activation is neces
sary and sufficient for certain LET-23 functions. We show that an inos
itol trisphosphate receptor can act as a PAS-independent, tissue-speci
fic positive effector of LET-23. Moreover, an inositol trisphosphate k
inase negatively regulates this transduction pathway. Signals transduc
ed by LET-23 control ovulation through changes in spermathecal dilatio
n, possibly dependent upon calcium release regulated by both IP3 and I
P4. Our results demonstrate that one mechanism by which receptor tyros
ine kinases can evoke tissue-specific responses is through activation
of distinct signal transduction cascades in different tissues.