The scaffolding protein Cnk Interacts with Alk to Promote Visceral Founder Cell Specification inDrosophila

ABSTRACT In Drosophila , the receptor tyrosine kinase Alk and its ligand Jeb are required to drive founder cell (FC) specification in the visceral mesoderm (VM). Alk-signalling activates downstream MAPK/ERK- and PI3K-pathways in human and Drosophila but little is known about immediate downstream signalling events. Here we report that the scaffolding protein Cnk interacts directly with Alk via a novel c-terminal binding motif. Cnk is required for Alk-signalling as ectopic expression of the minimal interaction motif as well as loss of maternal and zygotic cnk blocks visceral FC-formation, resembling the phenotype of jeb and Alk mutants. We also show that the Cnk-interactor Aveugle/Hyphen (Ave/HYP) is critical, while the (pseudo-) kinase Ksr is not required for Alk-signalling in the developing VM. Taken together, Cnk and Ave represent the first molecules downstream of Alk whose loss genocopies the lack of visceral FC-specification of Alk and jeb mutants indicating an essential role in Alk-signalling.