Enzyme substrate competition in a developing

Enzyme substrate competition in a
developing embryo
Yoosik Kim*, Mathieu Coppey, and Stanislav Y. Shvartsman
Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics,
Princeton University, Princeton, NJ 08544, USA.
Rona Grossman and Ze’ev Paroush
Department of Developmental Biology and Cancer Research, Institute for Medical
Research – Israel-Canada, The Hebrew University-Hadassah Medical School, PO Box
12272, Jerusalem 91120, Israe
Leiore Ajuria and Gerardo Jiménez
Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i
Estudis Avançats, Parc Científic de Barcelona, Barcelona 08028, Spain.
Session 3, Talk 1 (1:40 PM)
Whereas certain enzymes exhibit remarkable substrate specificity, others are quite
promiscuous. Among kinases, for example, D-fructokinase phosphorylates only one
substrate (D-fructose), yet protein kinases can have hundreds of substrates [1]. A key
question for such enzymes is whether their multiple substrates are processed in an
ordered fashion or concurrently, in a regime where they compete for access to a common
regulator. While cells have evolved a number of strategies for avoiding competitive
effects to ensure ordered substrate processing [2], substrate competition can be beneficial;
for example, for generating thresholds in cell cycle control [3]. Here we propose that
competitive effects can also provide a mechanism for integration of patterning signals in
embryonic development. Based on genetic and imaging experiments, we argue that in the
early Drosophila embryo multiple substrates of the Mitogen Activated Protein Kinase
(MAPK) compete for this enzyme. As a consequence, the signaling activity of MAPK
becomes dependent on the levels of its substrates. The resulting substrate competition
network provides a new mechanism for spatial integration of the maternal morphogen
gradients [4]. Competitive effects may play a more general role in spatial regulation of
signaling networks, where enzymes, such as MAPK, interact with their multiple
regulators and targets.
[1] Ubersax, J. A. and Ferrell, J. E., Nature Reviews Molecular Cell Biology 8, 530 (2007).
[2] Sullivan, M. and Morgan, D. O. Nature Reviews Molecular Cell Biology 8, 894 (2007).
[3] Bhattacharyya, R. P., Remenyi, A., Yeh, B. J., and Lim, W. A. Annual Review of Biochemistry 75, 655
[4] St Johnston, D. and Nusslein-Volhard, C. Cell 68 (2), 201 (1992).