During development of the hermaphrodite vulva, three out of six equivalent Pn.p cells in the ventral hypodermis are in- duced by a signal from the neighboring gonadal anchor cell to assume vulval cell fates. This signal is transduced in P6.p by an evolutionary conserved receptor tyrosine kinase/ras pathway where it specifies the primary cell fate. P6.p then induces adjacent cells (P5.p and P7.p) by a lateral signal to undergo the secondary fate. The
lin-2 gene is a component of the signal transduction pathway that specifies the primary fate, since loss of
lin-2 function causes the same vulvaless phenotype that is observed in the absence of the
let-23 receptor or after ablation of the anchor cell. We have cloned the
lin-2 gene and isolated cDNAs covering the whole predicted open reading frame. LIN-2 shows extensive sequence similarity to cell junction proteins such as mammalian ZO-1, the postsynaptic density protein PSD-95 or Drosophila Discs- Large. In addition, LIN-2 contains two kinase domains: a calcium/calmodulin dependent Ser/Thr kinase at the N-termi- nus and a guanylate kinase at the C-terminus. Site-directed mutagenesis of a
lin-2 minigene demonstrated that neither of the two kinase activities is required for
lin-2 function. Mosaic analysis indicated that
lin-2 is required in P6.p for the expression of the primary cell fate and production of the lateral signal. Our results exclude the possibility that LIN-2 acts as a Ser/Thr kinase in a signaling pathway in parallel to LET- 60/RAS or that guanylate kinase activity is required for the activation of the LET-60/RAS pathway. We propose that LIN-2 is a structural component of the Pn.p cell junctions that is required for efficient activation of the LET-23 receptor.