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 PAS-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.