Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online January 19, 2006
Science DOI: 10.1126/science.1120941

Research Articles

Submitted on October 4, 2005
Accepted on December 21, 2005

The Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway

Roby P. Bhattacharyya 1, Attila Reményi 2, Matthew C. Good 1, Caleb J. Bashor 3, Arnold M. Falick 4, Wendell A. Lim 2*

1 Department of Cellular and Molecular Pharmacology; Program in Biological Sciences
2 Department of Cellular and Molecular Pharmacology
3 Department of Cellular and Molecular Pharmacology; raduate Group in Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.
4 Howard Hughes Medical Institute Mass Spectrometry Laboratory, University of California, Berkeley, 17 Barker Hall, Berkeley, CA 94720, USA.

* To whom correspondence should be addressed.
Wendell A. Lim , E-mail: lim{at}cmp.ucsf.edu

Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We have found that the Ste5 scaffold has a more active role in the yeast mating pathway: a fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein (MAP) kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop (pTyr). Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
New Connections, New Components, Real Dynamics.
J. S. Bader (2009)
Science Signaling 2, pe48
   Abstract »    Full Text »    PDF »
Distal Recognition Sites in Substrates Are Required for Efficient Phosphorylation by the cAMP-Dependent Protein Kinase.
S. J. Deminoff, V. Ramachandran, and P. K. Herman (2009)
Genetics 182, 529-539
   Abstract »    Full Text »    PDF »
Disentangling the Complexity of Mitogen-Activated Protein Kinases and Reactive Oxygen Species Signaling.
A. Pitzschke and H. Hirt (2009)
Plant Physiology 149, 606-615
   Full Text »    PDF »
Protein Kinase Activation Loop Autophosphorylation in Cis: Overcoming a Catch-22 Situation.
P. A. Lochhead (2009)
Science Signaling 2, pe4
   Abstract »    Full Text »    PDF »
Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence.
L. S. Garrenton, A. Braunwarth, S. Irniger, E. Hurt, M. Kunzler, and J. Thorner (2009)
Mol. Cell. Biol. 29, 582-601
   Abstract »    Full Text »    PDF »
A Scaffold Makes the Switch.
H. G. Dohlman (2008)
Science Signaling 1, pe46
   Abstract »    Full Text »    PDF »
Substrate Discrimination among Mitogen-activated Protein Kinases through Distinct Docking Sequence Motifs.
D. L. Sheridan, Y. Kong, S. A. Parker, K. N. Dalby, and B. E. Turk (2008)
J. Biol. Chem. 283, 19511-19520
   Abstract »    Full Text »    PDF »
Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase.
L. Yu, M. Qi, M. A. Sheff, and E. A. Elion (2008)
Mol. Biol. Cell 19, 1739-1752
   Abstract »    Full Text »    PDF »
Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics.
C. J. Bashor, N. C. Helman, S. Yan, and W. A. Lim (2008)
Science 319, 1539-1543
   Abstract »    Full Text »    PDF »
Mapping dynamic protein interactions in MAP kinase signaling using live-cell fluorescence fluctuation spectroscopy and imaging.
B. D. Slaughter, J. W. Schwartz, and R. Li (2007)
PNAS 104, 20320-20325
   Abstract »    Full Text »    PDF »
WNK1 Is a Novel Regulator of Munc18c-Syntaxin 4 Complex Formation in Soluble NSF Attachment Protein Receptor (SNARE)-mediated Vesicle Exocytosis.
E. Oh, C. J. Heise, J. M. English, M. H. Cobb, and D. C. Thurmond (2007)
J. Biol. Chem. 282, 32613-32622
   Abstract »    Full Text »    PDF »
Retrophosphorylation of Mkk1 and Mkk2 MAPKKs by the Slt2 MAPK in the Yeast Cell Integrity Pathway.
M. Jimenez-Sanchez, V. J. Cid, and M. Molina (2007)
J. Biol. Chem. 282, 31174-31185
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis.
X. Zhao, R. Mehrabi, and J.-R. Xu (2007)
Eukaryot. Cell 6, 1701-1714
   Full Text »    PDF »
Scaffold proteins confer diverse regulatory properties to protein kinase cascades.
J. W. Locasale, A. S. Shaw, and A. K. Chakraborty (2007)
PNAS 104, 13307-13312
   Abstract »    Full Text »    PDF »
Src Family Kinases Directly Regulate JIP1 Module Dynamics and Activation.
D. Nihalani, H. Wong, R. Verma, and L. B. Holzman (2007)
Mol. Cell. Biol. 27, 2431-2441
   Abstract »    Full Text »    PDF »
Multiple WASP-interacting Protein Recognition Motifs Are Required for a Functional Interaction with N-WASP.
F. C. Peterson, Q. Deng, M. Zettl, K. E. Prehoda, W. A. Lim, M. Way, and B. F. Volkman (2007)
J. Biol. Chem. 282, 8446-8453
   Abstract »    Full Text »    PDF »
Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry.
A. Chi, C. Huttenhower, L. Y. Geer, J. J. Coon, J. E. P. Syka, D. L. Bai, J. Shabanowitz, D. J. Burke, O. G. Troyanskaya, and D. F. Hunt (2007)
PNAS 104, 2193-2198
   Abstract »    Full Text »    PDF »
The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module.
N. Kannan, N. Haste, S. S. Taylor, and A. F. Neuwald (2007)
PNAS 104, 1272-1277
   Abstract »    Full Text »    PDF »
Ccpg1, a Novel Scaffold Protein That Regulates the Activity of the Rho Guanine Nucleotide Exchange Factor Dbs.
E. V. Kostenko, O. O. Olabisi, S. Sahay, P. L. Rodriguez, and I. P. Whitehead (2006)
Mol. Cell. Biol. 26, 8964-8975
   Abstract »    Full Text »    PDF »
Interacting JNK-docking Sites in MKK7 Promote Binding and Activation of JNK Mitogen-activated Protein Kinases.
D. T. Ho, A. J. Bardwell, S. Grewal, C. Iverson, and L. Bardwell (2006)
J. Biol. Chem. 281, 13169-13179
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)