The candidate MAP kinase phosphorylation substrate DPL-1 (DP) promotes expression of the MAP kinase phosphatase LIP-1...

The highly-conserved, commonly used MAP kinase signaling cascade plays multiple integral roles in germline development in Caenorhabditis elegans. Using a functional proteomic approach, we found that the transcription factor DPL-1, a component of the LIN-35(Rb)/EFL-1(E2F)/DPL-1(DP) pathway, is a candidate phosphorylation substrate of MAP kinase. Moreover, dpl-1 genetically interacts with mpk-1(MAP kinase) to control chromosome morphology in pachytene of meiosis I, as does lin-35. However, EFL-1, the canonical DPL-1 heterodimeric partner, does not have a role in this process. Interestingly, we find that DPL-1 and EFL-1, but not LIN-35, promote the expression of a negative regulator of MPK-1, the MAP kinase phosphatase LIP-1. Two E2F consensus motifs are present upstream of the lip-1 open reading frame. Therefore, the Rb/E2F/DP pathway intersects with MAP kinase signaling at multiple points to regulate different aspects of C. elegans germ cell development. These two highly conserved pathways with major regulatory roles in proliferation and differentiation likely have multiple mechanisms for cross-talk during development across many species.