High impact information on hep

• Further, hep is required for expression in the dorsal epithelium edges of another dorsal closure gene, puckered [1].
• hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement [1].
• Here, we show that the small GTPases Dcdc42, Drac1, and the Hep JNKK control dpp expression in this migratory process [2].
• Dorsal closure can also be blocked by dominant negative Drosophila cdc42, which has been shown to act upstream of JNKK in vertebrates [3].
• DJNK is phosphorylated and activated by the Drosophila MAP kinase kinase HEP [4].

Biological context of hep

• MKK7 is most similar to the mediator of morphogenesis, hemipterous (hep), in Drosophila [5].
• Defects observed in mutant embryos, and adults with reduced Fos expression, are reminiscent of phenotypes caused by 'loss of function' mutations in the Drosophila JNKK homologue, hemipterous [6].
• Six putative JNKK kinase (JNKKK) family members are present in the fly genome, which could activate the core module in response to distinct stimuli [7].

Anatomical context of hep

• We show that hep controls the expression of puckered (puc) in the follicular epithelium in a cell-autonomous manner [8].
• By contrast, constitutively active hopscotch and hemipterous give massive activation of lamellocyte formation with little or no increase in total hemocyte numbers [9].

Regulatory relationships of hep

• In this report, we demonstrate that Drosophila TAK1 functions as both the Drosophila IkappaB kinase-activating kinase and the JNK kinase-activating kinase [10].

Other interactions of hep

• The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK) [11].
• Furthermore, we show that the small GTPase Dcdc42, but not Drac1, is an activator of puc expression in a hep-dependent manner in imaginal discs [12].
• Consistent with these observations, expression of LF in Drosophila inhibited the Hep/c-Jun N-terminal kinase pathway during embryonic dorsal closure and the related process of adult thoracic closure [13].
• Further, dMLK directly phosphorylates Hep, dMKK4 and also their mammalian counterparts, MKK7 and SEK1, in an in vitro kinase assay [14].

References