Research
Areas:
Cell Signaling, Developmental Biology
and Bioinformatics.
Research Interests:
Identifying novel signaling proteins
that control cell growth and tissue/organ development.
Current Projects:
Molecular recognition forms the
basis for all cellular events- from a simple bimolecular enzymatic
reaction to the cascades of multimeric protein complex in cell signaling.
Fundamental to the struc-ture and function of a protein is its “domain”-
a discrete, minimal modular entity that constitutes one of the basic
physical and functional unit of the polypeptide. This protein domain
can either serve as a protein docking/interaction site or an active
unit, where reactive residues take part in certain enzymatic reaction.
In some cases, they can also act as regulatory switches, where they
could influence the conformation, hence the recognition or activity
of the protein it resides. With the emphasis on functional genomics,
it is important to address what role does each of these domains
play and how their potential functions can be regulated.
One of the protein domains
that our group first identified and characterized is a novel protein
domain termed BCH domain, for BNIP-2 and Cdc42GAP Homology. This
unique protein domain is about 145 amino acids in length and was
initially known to be conserved in two proteins: BNIP-2 and Cdc42GAP.
We showed that BCH domain of BNIP-2 could act as a non-canonical
GTPase-activating protein (GAP) domain with a novel arginine finger
motif for the small GTPase, Cdc42, where it could also form a homophilic
association with itself and heterophilic complex with Cdc42GAP.
This complex negatively regulates their respective GAP activity.
To explore the frequency, distribution and also the potential roles
of BCH domains in other proteins, we aimed at studying more novel
members of proteins that harbor such domain. My group has identified
many proteins of unique BCH distribution. Many of these are already
cloned and being investigated with respect to their roles in cell
growth/death, differentiation, migration, and tissue/organ development.
As part of my group’s interest to link the cell signalling
event to the processes of developmental biology, we plan to study
signaling involved in liver biology and liver cancer using zebrafish,
Danio rerio, as the animal model. Liver is a major organ involved
in various metabolisms of protein and carbohydrate, storage of fuels,
vitamins, and also for the synthesis of most blood components and
elimination of all toxic substances from the blood. It is therefore
not surprising that any malfunc-tioning of this organ, either by
extrinsic factors such as viral infection or intrinsic gene mutations,
would result in various serious outcomes to our bodily function.
The zebrafish has recently become a very popular vertebrate model
of many human diseases, but very little has been worked on in the
liver cell signalling in this organism. This is part of the new
initiative “The Zebrafish Liver Program” that is established
at the Department of Biological Sciences.
Selected Publications:
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Low,B.C., Lim,Y.P., Lim, J., Wong,E.S., Guy,G.R.
(1999) Tyrosine phosphorylation of the Bcl-2-associated protein
BNIP-2 by fibroblast growth factor receptor-1 prevents its
binding to Cdc42GAP and Cdc42. J. Biol Chem.,
274(46):33123-33130.
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Low,B.C., Seow,K.T., Guy,G.R. (2000) The BNIP-2
and Cdc42GAP homology domain of BNIP-2 mediates its homophilic
association and heterophilic interaction with Cdc42GAP. J.
Biol. Chem., 275:37742-37751.
-
Zhou,Y.T., Soh,U.J., Shang,X., Guy,G.R., Low,
B.C. (2002) The BNIP-2 and Cdc42GAP homology/Sec14p-like domain
of BNIP-Sa is a novel apoptosis-inducing sequence. J.
Biol. Chem., 277:7483-92.
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Shang,
X., Zhou, Y.T. and Low B.C (2003). Concerted regulation of
cell dynamics by BNIP-2 and Cdc42GAP Homology/Sec14p-like,
proline-rich and GTPase-activating protein domains of a novel
Rho GTPase activating protein, BPGAP1. Journal of Biological
Chemistry 278:45903-45914.
-
Lua, B.L. and Low, B.C. (2004) Filling the
GAP in Cell Dynamics Control: BPGAP1 promotes cortactin translocation
to the cell periphery for enhanced cell migration. Biochemical
Society Transactions32:1110-1112.
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Lua, B. L. and Low, B.C (2004) BPGAP1 interacts
with cortactin and facilitates its translocation to cell periphery
for enhanced cell migration Molecular Biology of the
Cell 15:2873-2883.
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Zhou, Y.T., Guy, G.R. and Low, B.C. (2005)
BNIP-2 induces cell elongation and membrane protrusions by
interacting with Cdc42 via a unique Cdc42-binding motif within
its BNIP-2 and Cdc42GAP Homology domain. Experimental
Cell Research 303(2):263-274.
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Lua, B. L., and Low, B.C. (2005). Cortactin
phosphorylation as a switch for actin cytoskeletal network
and cell dynamics control. FEBS Letter Review 579:
577-585.
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Low, B. C. and Gong, Z. (2005) Reporter Gene
System: Green Fluorescent Proteins. Encyclopedia. Mol.
Cell Biol. and Mol. Med. Invited review article. Edited
by Robert A. Meyers. ISBN: 3-527-30542-4. (http://www.wiley-vch.de/books/emcbmm/index.html
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Lua, B. L. and Low, B. C. (2005) Activation
of EGFR endocytosis and ERK1/2 activation by BPGAP1 requires
its direct interaction with EEN/endophilin II and a functional
RhoGAP domain. Journal of Cell Science 118:
2707-2721.
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Zhang, B., Q. Cao, AC Guo, Q.D. Hu, H.Y.
Chu, Y.G. Chan, J.P. Buschdorf, B.C. Low, E.A. Ling and F.Y.
Liang (2005) Juxtanodin: an oligodendroglial protein that promotes
cellular arborization and 2',3'-cyclic nucleotide-3'-phosphodiesterase
trafficking. Proc Natl Acad Sci U S A. 102(32):11527-32.
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Zhu, S., Liu, L., Korzh, V., Gong, Z. and
Low, B. C (2006) RhoA acts downstream of Wnt5 and Wnt11 to
regulate convergence and extension movements by involving effectors
Rho Kinase and Diaphanous: use of zebrafish as an in vivo mode
l for GTPase signaling. Cellular Signaling 2006
Mar;18(3):359-372. Epub 2005 Jul 14
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Zhou,Y.T., Guy,G.R., Low, B. C (2006) BNIP-S
induces cell rounding during apoptosis by sequestering p50RhoGAP
and facilitating RhoA activation via its unique motifs in the
BNIP-2 and Cdc42GAP Homology domain Oncogene 25(16):2393-408.
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Buschdorf, J.P., Chew, L.L., Zhang, B.,
Cao, Q., Liang, F-Y., Liou, Y-C., Zhou, Y.T., Low, B.C (2006)
Brain-specific BNIP-2-Homology (BNIP-H) protein/Caytaxin
relocalizes glutaminase to neurite terminals and reduces the
levels of glutamate. Journal of Cell Science 119:3337-50
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Tang, Z.Q., Han, L.Y, Lin, H.H, Cui, J, Jia,
J., Low, B.C., Li, B.W. and Chen, Y.Z. 2007 Derivation of stable
microarray cancer-differentiating signatures using consensus
scoring of multiple random sampling and gene-ranking consistency
evaluation. Cancer Res. 67(20):9996-10003.
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Zhu, S., Korzh, V., Gong, Z. and Low, B. C
(2007) RhoA prevents apoptosis during zebrafish embryogenesis
through activation of Mek/Erk pathway. Oncogene.
2007 Sep 17; [Epub ahead of print]
Recent Awards
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A*STAR-Singapore National Academy of Science
Young Scientist Award (2003)
-
Teaching Excellence Award, Faculty of Science,
NUS (2003)
-
Who’s Who in Science and Engineering
(Marquis, 7th Edition; 2003)
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A*STAR Biomedical Research Council (BMRC) Young
Investigator Award, Singapore (2002)
-
Finalist for A*STAR-Singapore
National Academy of Science Young Scientist Award (2000, 2001)
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