CoChat
Sign Up
Cited by 95Protein Kinase Regulation and GTPase SignalingCellular transport and secretionProtein Tyrosine Phosphatases

Crystal structure of the p14/MP1 scaffolding complex: How a twin couple attaches mitogen-activated protein kinase signaling to late endosomes

Open access
Kurzbauer, Robert, Teis, David, de Araujo, Mariana E. G., Maurer-Stroh, Sebastian, Eisenhaber, Frank, Bourenkov, Gleb P., Bartunik, Hans D., Hekman, Mirko +3 more·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0403435101PMC PMC503730
Open this paper in CoChat — free account

Abstract

Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which are coordinated by scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand the spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight ( K d = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-Å crystal structure of a biologically functional p14/MP1 complex. The overall topology of the individual MP1 and p14 proteins is almost identical, having a central five-stranded β-sheet sandwiched between a two-helix and a one-helix layer. Formation of the p14/MP1 heterodimer proceeds by β-sheet augmentation and yields a unique, almost symmetrical, complex with several potential protein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative to the endosomal membrane. Two highly conserved and hydrophobic protein-binding sites are located on the opposite “cytoplasmic” face of the p14/MP1 heterodimer and might therefore function as docking sites for the target proteins extracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence analyses revealed that MP1/p14, together with profilins, define a protein superfamily of small subcellular adaptor proteins, named ProflAP. Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0403435101

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The structures of LAMTOR2, LAMTOR3 and LAMTOR5 revealed roadblock folds for the individual LAMTOR3 and LAMTOR5 monomers and the formation of MP1/p14 heterodimers by edge-to-edge juxtaposition of the roadblock domains.

    “The structures of LAMTOR2, LAMTOR3 and LAMTOR5 were the first to be characterized prior to the discovery of the Ragulator complex (Kurzbauer et al., 2004; Cui et al., 2008; Lunin et al., 2004; Qian et al., 2005; Garcia-Saez et al., 2011), revealing roadblock folds for the individual LAMTOR3 and LAMTOR5 monomers, and the formation of MP1/p14 heterodimers by edge-to-edge juxtaposition of the roadb”

    From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Kurzbauer et al., 2004

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 29

  1. [1]Pawson, T. & Scott, J. D. (1997) Science 278, 2075–2080. [DOI] [PubMed] [Google Scholar]
  2. [2]Morrison, D. K. & Davis, R. J. (2003) Annu. Rev. Cell Dev. Biol. 19, 91–118. [DOI] [PubMed] [Google Scholar]
  3. [3]Pawson, T. (2004) Cell 116, 191–203. [DOI] [PubMed] [Google Scholar]
  4. [4]Chang, L. & Karin, M. (2001) Nature 410, 37–40. [DOI] [PubMed] [Google Scholar]
  5. [5]Garrington, T. P. & Johnson, G. L. (1999) Curr. Opin. Cell Biol. 11, 211–218. [DOI] [PubMed] [Google Scholar]
  6. [6]Kolch, W. (2000) Biochem. J. 351, 289–305. [PMC free article] [PubMed] [Google Scholar]
  7. [7]Choi, K. Y., Satterberg, B., Lyons, D. M. & Elion, E. A. (1994) Cell 78, 499–512. [DOI] [PubMed] [Google Scholar]
  8. [8]Elion, E. A. (2001) J. Cell Sci. 114, 3967–3978. [DOI] [PubMed] [Google Scholar]
  9. [9]Therrien, M., Wong, A. M. & Rubin, G. M. (1998) Cell 95, 343–353. [DOI] [PubMed] [Google Scholar]
  10. [10]Schaeffer, H. J. & Weber, M. J. (1999) Mol. Cell. Biol. 19, 2435–2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. [11]Morrison, D. K. (2001) J. Cell Sci. 114, 1609–1612. [DOI] [PubMed] [Google Scholar]
  12. [12]Muller, J., Ory, S., Copeland, T., Piwnica-Worms, H. & Morrison, D. K. (2001) Mol. Cell 8, 983–993. [DOI] [PubMed] [Google Scholar]
  13. [13]Roy, F., Laberge, G., Douziech, M., Ferland-McCollough, D. & Therrien, M. (2002) Genes Dev. 16, 427–438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [14]Schaeffer, H. J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A. & Weber, M. J. (1998) Science 281, 1668–1671. [DOI] [PubMed] [Google Scholar]
  15. [15]Wunderlich, W., Fialka, I., Teis, D., Alpi, A., Pfeifer, A., Parton, R. G., Lottspeich, F. & Huber, L. A. (2001) J. Cell Biol. 152, 765–776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. [16]Teis, D., Wunderlich, W. & Huber, L. A. (2002) Dev. Cell 3, 803–814. [DOI] [PubMed] [Google Scholar]
  17. [17]Teis, D. & Huber, L. A. (2003) Cell. Mol. Life Sci. 60, 2020–2033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. [18]Otwinowski, Z. & Minor, W. (1997) Methods Enzymol. 276, 307–326. [DOI] [PubMed] [Google Scholar]
  19. [19]La Fortelle, E. & Bricogne, G. (1997) Methods Enzymol. 276, 472–494. [DOI] [PubMed] [Google Scholar]
  20. [20]Abrahams, J. P. & Leslie, A. G. W. (1996) Acta Crystallogr. D 52, 30–42. [DOI] [PubMed] [Google Scholar]
  21. [21]Brunger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., et al. (1998) Acta Crystallogr. D 54, 905–921. [DOI] [PubMed] [Google Scholar]
  22. [22]Engh, R. A. & Huber, R. (1991) Acta Crystallogr. A 47, 392–400. [Google Scholar]
  23. [23]Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. (1991) Acta Crystallogr. A 47, 110–119. [DOI] [PubMed] [Google Scholar]
  24. [24]Kraulis, P. J. (1991) J. Appl. Crystallogr. 24, 946–950. [Google Scholar]
  25. [25]Merritt, E. A. & Bacon, D. J. (1997) Methods Enzymol. 277, 505–524. [DOI] [PubMed] [Google Scholar]
  26. [26]Sanner, M. F., Olson, A. J. & Spehner, J. C. (1996) Biopolymers 38, 305–320. [DOI] [PubMed] [Google Scholar]
  27. [27]Bashford, D. & Gerwert, K. (1992) J. Mol. Biol. 224, 473–486. [DOI] [PubMed] [Google Scholar]
  28. [28]Tanoue, T., Adachi, M., Moriguchi, T. & Nishida, E. (2000) Nat. Cell Biol. 2, 110–116. [DOI] [PubMed] [Google Scholar]
  29. [29]Pei, J. & Grishin, N. V. (2001) Bioinformatics 17, 700–712. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Kurzbauer, R., Teis, D., de Araujo, M. E. G., Maurer-Stroh, S., Eisenhaber, F., Bourenkov, G. P., Bartunik, H. D., Hekman, M., Rapp, U. R., Huber, L. A., & Clausen, T.
Affiliations
  • Innsbruck Medical University (AT)
  • Institute for Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria; Department for Histology and Molecular Cell Biology, Medical University of Innsbruck, Müllerstrasse 59, A-6020 Innsbruck, Austria; Max-Planck-Arbeitsgruppen für Strukturelle Molekularbiologie, Deutsches Elektronen-Synchrotron, Notkestrasse 85, D-22603 Hamburg, Germany; and Institute for Medical Radiation and Cell Research, University of Würzburg, Würzburg 97078, Germany
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-07-19
Volume
101
Issue
30
Pages
10984-10989
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0403435101
PMC
PMC503730
OpenAlex
W2127489458
Cited by
95
References
31
Citations by year
2025: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 9 · 2012: 8
FWCI
2.97
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
p14, scaffold proteins, adaptor proteins, MAPK signaling, late endosomes, heterodimer, crystal structure, beta-sheet, profilin, protein superfamilies
MeSH terms
Animals, Carrier Proteins, Cell Line, Cloning, Molecular, Cricetinae, HeLa Cells, Humans, Membrane Proteins, Models, Molecular, Phosphorylation, Proteins, Endosomes, Recombinant Proteins, Signal Transduction, Polymerase Chain Reaction, Sequence Deletion, Protein Structure, Secondary, Crystallography, X-Ray, Mitogen-Activated Protein Kinases, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review