Greatwall kinase

Abstract

Mutations in the Drosophila gene greatwall cause improper chromosome condensation and delay cell cycle progression in larval neuroblasts. Chromosomes are highly undercondensed, particularly in the euchromatin, but nevertheless contain phosphorylated histone H3, condensin, and topoisomerase II. Cells take much longer to transit the period of chromosome condensation from late G2 through nuclear envelope breakdown. Mutant cells are also subsequently delayed at metaphase, due to spindle checkpoint activity. These mutant phenotypes are not caused by spindle aberrations, by global defects in chromosome replication, or by activation of a caffeine-sensitive checkpoint. The Greatwall proteins in insects and vertebrates are located in the nucleus and belong to the AGC family of serine/threonine protein kinases; the kinase domain of Greatwall is interrupted by a long stretch of unrelated amino acids.

Genes required for Drosophila nervous system development identified by RNA interference

“…Data from a screen for gain-of-function mutants suggested that gwl is involved in motor axon guidance and synaptogenesis in larvae (29). More recently, gwl loss-offunction mutations that result in mitotic delay in larval neuroblasts and defective condensation of chromosomes in Drosophila cell cultures have been described (30). Embryos injected with gwl dsRNA lack some commissures, have breaks in the longitudinal connectives, and lack some segmental nerves ( Fig.…”

Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis

“…Meanwhile, a novel mitotic kinase important for proper timing of G2 -M transitions called Greatwall (GW) was discovered in Drosophila [46]. Subsequent work with Xenopus egg extracts revealed that GW is required for both establishment and maintenance of M phase [47,48].…”

Regulation of Greatwall kinase by protein stabilization and nuclear localization

“…It has been reported that both human and Drosophila Gwl localized in the nucleus during interphase, [17][18][19] whereas in Xenopus oocytes Gwl appeared predominantly cytoplasmic. 8 To investigate the subcellular localization of Gwl in Xenopus cells, we tagged the WT or G41S Gwl with DsRed, and expressed the recombinant proteins in Xenopus S3 cells harboring stable expression of GFP-a-tubulin.…”