Supplementary Material Table 5- Drosophila protein kinases with cell cycle phenotypes
and their putative orthologues.
Name /Link Putative Orthologues
Previously Known Functionsa
(Human, Drosophila, C.elegans; S.pombe, S.cerevisae)
to FlyBase Link to InParanoid
database
Nonreceptor tyrosine kinase – effector of cdc42 1; dorsal closure, expressed highly in mitotic
Ack
HS-Ack1
domains2
Regulates entry into mitosis; centrosome maturation and spindle formation; mutants display
aurA
HS-Aurora A
defects in centrosome and spindle behaviour3
aurora B HS-AurB*; SC-Ipl1p* Chromosome alignment & spindle assembly checkpoint & cytokinesis; chromosome
condensation & cytokinesis3
BubR1
HS-BubR1; SC-Bub1 Spindle assembly checkpoint4;spindle assembly checkpoint-similar role to S. cerevisiae mad3 ;
contains KEN box5, mutants show lower MI and faster exit from mitosis6
cdc2
HS-CDK1; SC-cdc28; Regulates G2 to M-phase transition and entry to mitosis7; activation of the APC8; G2/M transition
SP-cdc2
of mitotic cycle9
G1/S transition and S phase progression; G1/S transition and S phase
cdc2c
HS CDK2
G1/S transition; Cell growth10,11
Cdk4
HS-CDK6/4
Regulation of RNA polymerase 212
Cdk8
HS-CDK8
Interacts with pRb13. Regulation of RNA polymerase 214
Cdk9
HS-CDK9
Cytokinesis15; cytokinesis16
CG10522 HS-CIT
HS-ULK2; CE-Unc- Axon morphogenesis and elongation, may signal through ras17
51
Cell spreading and motility - colocalises with ezrin in lamellipodia18
CG1344
HS-Pace-1;CSSCY1*
CG14030/ HS-BUB1*; SC-Bub1 Spindle assembly checkpoint; Does not contain KEN box; functionally similar to HS Bub1 and SC
BUB1
Bub15
CG15072 HS-KIAA0999/QSK AMPk-related kinase activated by LKB19
NTKL localises to the centrosomes during mitosis20
CG1951
HSKIAA1360;NTKL*;SC
-SCY1
Activated by SRC21
CG2309
HS-ERK8
Chromatin assembly following DNA replication; DNA damage checkpoint target22; essential for
CG2829
HS-TLK1/2
nuclear divisions, cell viability and chromatin assembly23.
CG3216
HS-Atrial natriuretic G-protein coupled receptor protein signaling pathway- respond to cGMP24 ; may inhibit
proliferation25
peptide receptor *
CG10967
Cdc7-related kinase - DNA replication26
Similarity to leucine-rich repeat kinase (LRRK1)
MAST2 localizes to spermatid manchette through other MAPS; activates NFKB (Mus
musculus)27,28
CG7094
HS-CSNK1A1*; CE- Wnt signalling29
kin-19*
Novel RSKL similar to JIL, S6K and S6KII
CG7156
HS-RSK-LIKE
PROTEIN
Cdc2-related kinase 1; involved in gliosis30
CG7236
HS-CDKL1
CG7597
HS-CRK7/CDC2L5; Cdc2-related protein kinase 7; MPM-2 antigen-possibly involved in splicing and transcription31;
CE-B0285.1
RNAi mutants show slow developmental growth32
CG7643
HS-TTK; SC-MPS1 Spindle assembly checkpoint33 and centrosome duplication34; duplication of spindle pole bodies &
spindle assembly checkpoint4
Pre-mRNA splicing machinery; phosphorylate SR proteins; SPK-1, required for embryogenesis and germline
CG8565
HS-SRPK2*; CESPK-1*
development35
Extracellular matrix remodelling36,37
CG9488
HS-DDR2*
CkIalpha HS-CSNK1A1
Interacts with Axin to inhibit JNK cascade; promotes armadilllo degradation38; induced after DNA
damage39
CkIIalpha HS-CK2A1;SC-CKA1 Associated with APC - phosphorylates p53; multiple signalling pathways40; circadian clock
Up-regulated in ovarian cancer41; Interacts genetically with drl
dnt
HS-RYK
Lammer dual specificity kinase 2; meiotic progression42; septation and proliferation43
Doa
HS-CLK2/3/4; SPLkh1
Receptor tyrosine kinase; axon pathfinding; Wnt receptor signalling pathway
drl
HS-RYK
PFTAIRE (cdc2-related) protein kinase 1; Ecdysone-induced protein 63E required for embryonic
Eip63E
HS-PFTAIRE-1
and larval development
NO/cGMP/cGK signaling - negative regulator of cell proliferation44;response to hypoxia;
for
HS-PRKG1
behaviour
fray
HS-OSR1 or SPAK Oxidative stress response- phosphorylates PAK1; MAP4K in JNK pathway45; Nerve ensheathment
fs(1)h
HS-BRD4/MCAP or BRD4 associates with chromosomes and injection of antibodies arrests cells in G2/M 46; RING3 is
linked to human leukaemia; trans-activates genes dependent on E2F47
RING3*
Gcn2
HS-GCN2; SC-GCN2 Phosphorylates eIF2alpha in amino acid deprivation, signalling the activation of NFKB 48; protein
synthesis in stress response
gek
HSCDC42BP;CEAbnormal accumulation of F actin in oogenesis; RNAi gives dumpy & slow growing embryos
K08B12.5.
gish
HS-CK1G3;CEGlial cell migration; Mitotic spindle orientation49; growth and division - cell morphogenesis and cytokinesis50.
Y106G6E.6;SCYCK1 or 2
Replication and DNA damage G2 checkpoint51; cell cycle coordination in syncytial embryo;
grp
HS-Chk1
mutants show rapid entry into M, defects in chromosome condensation and degradation of cyclin
A
CG32742
CG5483
CG6498
HS-cdc7; SC-cdc7
HS-KIAA1790
HS-MAST1 or 2
1
gwl
hippo
hop
htl
ik2
Ilk
inaC
InR
Candidate gene for autosomal dominant thrombocytopenia on human chromosome 1052;
sporulation and meiosis53; cek1 is a suppressor of cut 8 (necessary for anaphase)54; mutants show
chromosome condensation defects55
HS-STK4 or 3; SC- Induction of apoptosis56; apoptosis- mutants have higher levels of cyclinE and DIAP1;mitotic exit
cdc15*
network57
JAK-STAT signalling; haemocyte proliferation & cell fate determination- interacts with CDK458
HS-JAK2/3/1
Receptor tyrosine kinase for FGFs; interacts with ras; important for cell migration in several
HS-FGR2/3/1/4
mesodermal lineages; pbl may act downstream of htl in regulating cell shape 59
NFK beta signalling; NFK beta signalling - defense response.
HS- NAK/TBK1
HS-ILK1 or ILK2; CE- Phosphorylates GSK-3 - connects integrins to actin cytoskeleton; upregulated in several
cancers60; focal adhesions of cytoskeleton
ILK
SC-PKC1
Mutants have behaviour defects; morphogenesis checkpoint61
Insulin-like growth factor I receptor-mediates cell proliferation; signals to MAPK/ras and to PI3K
HS-IGF1R
62
; mutants are long lived and have a smaller body
HS-FLJ14813; SCrim15; SP-cek1*
Activated by MAPK and SAPK/p38; phosphorylates CREB63; phosphorylation of Histone H364 ;
activation of NF-kappaB65; histone H3 phosphorylation; transcriptional control, maintenance of
chromatin structure66
Stress response-phosphorylates MAPK p3867; asymmetric development of the egg .
lic
HS-MAP2K3/6
Tumour suppressor - activates 13 kinases of the AMPK subfamily19; oocyte microtubule
lkb1
HS-lkb1
organization.
Activated in response to IFN in the p38 pathway68
MAPk-Ak2 HS-MAPKAPK2/3
Interacts with Cdc42 and Rac - promotes filopodium formation and cell migration69,70;cytoskeleton
mbt
HS-PAK7/5/4
& photoreceptor development
JAK-STAT and JNK cascades -links response to stress to cell cycle progression71
Mkk4
HS-MAP2K4
mnb
HS-DyrK1;CE-mbk1 Candidate target of Down’s Syndrome; mutants have small brains; spindle positioning and asymmetric cell
or 2*
division72
Negative regulator of CDK1; regulates mitotic entry
Myt1
HS-Myt1
nmo
HS-NemoLK; CEWnt signalling - polarization/rotation of cells - NFKB interactor; embryogenesis
W06F12.1
Muscle specific tyrosine kinase receptor; interacts with ras in oocytes
Nrk
HS-MUSK
Phosphorylates CDC25C regulating interaction with 14-3-373; regulator of oocyte cytoskeleton;
par-1
HS-MARK3
interacts genetically with lkb1; regulator of wnt signalling
Metabolism74; embryonic morphogenesis
HS-PHKG
PhK
Activation of p70s6k75; upstream effector of S6k76;Mutant cells are smaller.
Pk61C
HS-PDK1
Pk92B
HS-ASK1/MEKK5/1; Apoptosis77; stress & morphogenesis checkpoint 61
SC-Bck1*
Pka-C2
HM-PKA-Cbeta*; SC- Regulates mitotic progression through cdc2078
PKA1 or 2*
Mediates activation of NF-kappaB and MAPK pathways (JNK/p38)79; immunity
pll
HS-IRAK1
Multiple mitotic functions –cytokinesis80; multiple mitotic functions
polo
HS-plk1; SC-cdc5
Vascular endothelial growth factor receptor 1 precursor; regulation of proliferation and cell
Pvr
HS-VEGFR1/2/3
migration81; organisation of actin cytoskeleton in cell migration82
Cytokinesis83; tissue polarity
Rok
HS-ROCK
Cell proliferation and growth84; interacts with Pk61C,Tor & Akt1 – Mutants cells are smaller85
S6k
HS-RPS6KB1/2
Central nervous system development86; Phosphorylates tuberin inhibiting its ability to suppress
S6kII
HS-RSK3/2/1/46
mTor signalling87, Phosphorylation and inhibition of myt1 kinase 88-activates bub189 (Xenopus
laevis)
Required for mitosis (Mus musculus)90
SAK
HS-SAK
SNF1A
HS-AMPK2;SC-SNF1 metabolic stress response; regulation of pol II and initiation of meiosis91
Src64B
HS- FYN*
regulation of actin polymerisation; contraction of actin/myosin during cellularization 92; cell
proliferation93
TATA box binding protein associated – induces G1 progression through p5394; G2/M progression
Taf1
HS-TafII250
through transcriptional activation of string/cdc2595
tkv
HS-BMPR1B
Type I TGF receptor; cell growth and division - anterior/posterior patterning
JIL-1
HS-RPS6KA5/4
tor
Tor
HS-RET*
HS-FRAP1
trbl
wee
wts
Mutants show disruption in anterior/posterior axis; Activates ras and STAT 96
Target of rapamycin – regulates G1/S transition97; Mutant cells are smaller and arrest in G198;
growth control
SKIP3 is upregulated in human tumours99; Negative regulator of CDK1; Induces Proteolysis of
HS-trb2/1/SKIP3
string and twine100
HS-Wee1; SP-wee1* Mitotic checkpoint phosphorylation of CDK1; Wee1p phosphorylates Cdc2p on Tyr15101; regulates
mitotic entry
Tumour suppressor; inhibits G2/M and promotes apoptosis102; mutants show overgrowth and
HS-LATS1/2
abnormal morphogenesis; interacts genetically with CycA and cdc2
H. Sapiens (HS); C. elegans (CE); S. Cerevisiae (SC); S. Pombe (SP). We obtained
orthologues from other organisms in the Inparanoid database103 (confidence value=0.05 or
higher). We indicate the closest homologue after a BLAST104 search in NCBI, when the
orthology is not clear (entries with *). a-Information on Drosophila phenotypes was taken from
literature search and FlyBase (www.flybase.org). Information was also drawn from
2
WormBase(http://www.wormbase.org/), from the Budding Yeast Database (SGD)
(http://www.yeastgenome.org/) and from OMIM (Online Mendelian Inheritance of Men@
NCBI). Entries are shown in alphabetic order and more detail is given than in Table 1. Due to
limitations of space we regret that it is not possible to mention all published works relevant to
this table.
3
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