genghis khan: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

Gene name - genghis khan

Synonyms -

Cytological map position - 60B

Function - signaling protein

Keywords - cytoskeleton, oogenesis

Symbol - gek

FlyBase ID: FBgn0023081

Genetic map position -

Classification - similar to myotonic dystrophy protein kinase

Cellular location - potentially cytoplasmic



NCBI links: Precomputed BLAST | Entrez Gene
BIOLOGICAL OVERVIEW

Genghis khan (Gek) was isolated in a search for proteins that physically interact with Drosophila small GTPases Rac1 and Cdc42. The sought after protein was likely to be an effector of Drosophila Cdc42 because of its role in actin polymerization. The role of Cdc42 and other small GTPases (Rho and Rac) in cytoskeletal dynamics has remained something of a mystery. In mammalian fibroblasts these proteins regulate the actin polymerization that underlies the respective formation of stress fibers (Rho), lamellipodia (Rac), and filopodia (Cdc42). These proteins are also involved in the activation of kinase cascades and in the regulation of cell proliferation. Perturbations in the activity of these GTPases in yeast, flies, and mice result in the disruption of many biological processes, including yeast budding, axon and dendrite outgrowth, myoblast fusion, epithelial cell shapes, and tissue polarity establishment. Pak, a protein kinase effector for both Rac and Cdc42, functions in mitogen-activated protein kinase activation, but not in cytoskeleton regulation, suggesting that Pak is the effector for Rac and Cdc42 in the activation of the MAP kinase cascades. The effectors of Rac and Cdc42 for the regulation of actin polymerization have not yet been characterized (Luo, 1997 and references).

Mutants in gek are defective in oogenesis. Expression of constitutively active and dominant negative mutants of Drosophila Cdc42, as described in Murphy (1996), results in a defective cortical F-actin around nurse cells and free floating ring canal components, similar to what is observed in gek mutants. Egg chambers homozygous for gek mutations exhibit abnormal accumulation of F-actin and are defective in producing fertilized eggs. The F-actin rich ring canals between nurse cells and between the oocyte and the nurse cells are present in egg chambers mutant for gek. However, the cortical F-actin that surrounds the nurse cells appear abnormal, and ectopic F-actin blobs are frequently observed in the nurse cells and oocytes. The phenotypes caused by overexpressing dominant mutants of Cdc42, however, are more severe than those of gek mutants and are associated with a block in oogenesis at earlier stages of development, as compared with loss of function gek mutants. This raises the possibility that Gek is not the only effector for Cdc42 in regulating actin polymerization. Potential candidates for additional Cdc42 effectors include the recently identified WASP family of proteins (Luo, 1997).


GENE STRUCTURE

Transcript length - 5.1 kb


PROTEIN STRUCTURE

Amino Acids - 1613

Structural Domains

Gek is a large protein. The N-terminus of Gek contains a predicted Ser/Thr kinase catalytic domain. This is followed by a large coiled-coil domain with sequence homology to myosin heavy chain, a Cys-rich domain similar to the phorbol ester/diacylglycerol binding domain of protein kinase C, and a plekstrin homology domain, which is found in many signaling molecules and used for protein-lipid interactions and the recruitment to the cell surface. Near the Gek C terminus resides the sequence that resembles a Cdc42/Rac interactive binding (CRIB) domain. Indeed, deletion of three residues in Gek, which correspond to three conserved residues of the CRIB domain, disrupts Gek's binding to Cdc42 (Luo, 1997)


genghis khan: Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 15 January 98

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