title: Src kinases and ERK activate distinct responses to Stitcher receptor tyrosine kinase signaling during wound healing in Drosophila.
abstract: Metazoans have evolved efficient mechanisms for epidermal repair and survival following injury. Several cellular responses and key signaling molecules that are involved in wound healing have been identified in Drosophila, but the coordination of cytoskeletal rearrangements and the activation of gene expression during barrier repair are poorly understood. The Ret-like receptor tyrosine kinase (RTK) Stitcher (Stit, also known as Cad96Ca) regulates both re-epithelialization and transcriptional activation by Grainy head (Grh) to induce restoration of the extracellular barrier. Here, we describe the immediate downstream effectors of Stit signaling in vivo. Drk (Downstream of receptor kinase) and Src family tyrosine kinases bind to the same docking site in the Stit intracellular domain. Drk is required for the full activation of transcriptional responses but is dispensable for re-epithelialization. By contrast, Src family kinases (SFKs) control both the assembly of a contractile actin ring at the wound periphery and Grh-dependent activation of barrier-repair genes. Our analysis identifies distinct pathways mediating injury responses and reveals an RTK-dependent activation mode for Src kinases and their central functions during epidermal wound healing in vivo.
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
authors: Vasilios
authors: V
authors: Tsarouhas
authors: Liqun
authors: L
authors: Yao
authors: Christos
authors: C
authors: Samakovlis
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D010449:Peptide Mapping; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D062326:Re-Epithelialization; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C080530:drk protein, Drosophila; C062330:grh protein, Drosophila; C000593330:Cad96Ca protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C100382:Src42A protein, Drosophila; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Drk; Drosophila; ERK; RTK signaling; Src-family kinases; Stitcher; Wound healing