The Interactive Fly

Evolutionarily conserved developmental pathways

Stress activated and cell motility feedback pathway: The Jun-N-terminal kinase (JNK) activated MAP kinase cascade links the Rho family of GTP-binding proteins to transcription of Jun

Mitogen activated protein kinase (MAPK) cascades tranduce signals from multiple extracellular stimuli, mediating responses such as cell proliferation, differentiation, and the regulation of metabolic pathways. There are multiple MAPKs in eukaryotes. In Drosophila, two pathways have been identified. (1) MAPK (Rolled) is a component of the Ras pathway, and is required at least three times in development: for the terminal system mediating responses to the Torso receptor, for neurogenic and wing vein pathways mediating responses to the EGF-receptor, and for the differentiation of photoreceptors, mediating responses to the Sevenless receptor (See Neural induction pathway -Epidermal growth factor and its receptor, plus the Ras pathway, and ETStranscription factors).

(2) Another MAPK pathway in Drosophila involves the MAPK called Jun-N-terminal kinase (DJNK), also known as Basket. This second MAPK pathway also involves another kinase called Hemipterous that serves to phosphorylate DJNK. Both proteins are required for dorsal closure, the sealing of the dorsal region of the embryo late in embryonic development. Dorsal closure involves coordinate cell shape changes of ectodermal cells. (For a discussion of dorsal closure see Hemipterous ). The phosphorylation cascade involving HEP and DJUN terminates in the phosphorylation of DJUN. Both DJNK and DJUN are activated in the the immune response of the fly. DJNK is closely associated on chromosome 2 with dror, a Drosophila receptor tyrosine kinase homolog of vertebrate TRK kinases, which mediate responses to neurotropins. Close chromosomal linkage often, but not always, occurs as a consequence of shared developmental function.

In vertebrates and in Drosophila the Jun-N-terminal kinase (JNK) activated MAP kinase cascade transduces signals from Rac and Cdc-42, both members of the Rho family of GTP-binding proteins implicated in cell motility, cell adhesion, cytokinesis, cell morphology, and cell growth. It is thought that this cell mobility kinase cascade provides feedback information to the nucleus about changes in the cytoskeleton. In addition the JNK-MAP kinase cascade transduces stress related assaults such as bacterial infection to the nucleus, where these signals activate the immune response. Although the fly's immune response (See JNK for more information) does not have an immunoglobulin system, it shares with vertebrates an inducible system that is based on the need to detect and protect against danger.

Drosophila                        Homologs in other species ----------                        ----------------------------Rac (See JNK/Basket)              Mammalian: RacCdc-42 (See JNK/Basket)           Mammalian: Cdc-42DPAK (See Hemipterous)            Mammalian: p65PAKHemipterous                       Xenopus: XMEK2                                         Mammalian: MKK4 Basket/JNK                        Xenopus: JNK/SAPK                                   Mammalian: c-Jun NH2-terminal kinases (SAPKs/JNKs) DJun                              Mammalian: c-Jun

date revised: 14 Oct 96

Developmental Pathways conserved in Evolution

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