The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Transcriptional Cross-talk between Smad, ERK1/2, and p38 Mitogen-activated Protein Kinase Pathways Regulates Transforming Growth Factor-β-induced Aggrecan Gene Expression in Chondrogenic ATDC5 Cells
Open accessAbstract
In chondrogenesis, members of the transforming growth factor-beta (TGF-beta) superfamily play critical roles by inducing gene expression of cartilage-specific molecules. By using a chondrogenic cell line, ATDC5, we investigated the TGF-beta-mediated signaling pathways involved in expression of the aggrecan gene (Agc). At confluency, TGF-beta induced Agc expression within 3 h, and cycloheximide blocked this induction, indicating that de novo protein synthesis is essential for this response. At this stage, TGF-beta induced rapid, transient phosphorylation of Smad2, extracellular signal-activated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). Inhibition of the Smad pathways by transfection with a dominant negative Smad4 construct significantly reduced TGF-beta-induced Agc expression, indicating that Smad signaling is essential for this response. Furthermore, an inhibitor of the ERK1/2 pathway, U0126, or inhibitors of the p38 MAPK pathway, SB203580 and SKF86002, repressed TGF-beta-induced Agc expression in a dose-dependent manner, indicating that ERK1/2 or p38 MAPK activation is also required for TGF-beta-induced Agc expression in confluent ATDC5 cells. In differentiated ATDC5 cells, persistently high basal levels of ERK1/2 and p38 MAPK phosphorylation correlated with elevated basal Agc expression, which was inhibited by incubation with inhibitors of these pathways. Whereas Smad2 was rapidly phosphorylated by TGF-beta and involved in the initial activation of Agc expression in confluent cells, Smad2 activation was not required for maintaining the high level of Agc expression. Taken together, these results suggest an important role for transcriptional cross-talk between Smad and MAPK pathways in expression of early chondrocytic phenotypes and identify important changes in the regulation of Agc expression following chondrocyte differentiation.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
TGF-β signalling from cell membrane to nucleus through SMAD proteins
Heldin, C.-H., Miyazono, K., & ten Dijke, P. (1997) · Nature · doi:10.1038/37284 · Cited by 3,696
A protein kinase involved in the regulation of inflammatory cytokine biosynthesis
Lee, J. C., Laydon, J. T., McDonnell, P. C., Gallagher, T. F., Kumar, S., Green, D., McNulty, D., Blumenthal, M. J., Keys, J. R., Land vatter, S. W., et al. (1994) · Nature · doi:10.1038/372739a0 · Cited by 3,288
Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase
Favata, M. F., Horiuchi, K. Y., Manos, E. J., Daulerio, A. J., Stradley, D. A., Feeser, W. S., Van Dyk, D. E., Pitts, W. J., Earl, R. A., Hobbs, F., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18623 · Cited by 3,015
In VitroChondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells
Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M., & Yoo, J. U. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3858 · Cited by 2,382
TGFβ signals through a heteromeric protein kinase receptor complex
Wrana, J. L., Attisano, L., Cárcamo, J., Zentella, A., Doody, J., Laiho, M., Wang, X.-F., & Massague, J. (1992) · Cell · doi:10.1016/0092-8674(92)90395-s · Cited by 1,526
Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction
Yamaguchi, K., Shirakabe, K., Shibuya, H., Irie, K., Oishi, I., Ueno, N., Taniguchi, T., Nishida, E., & Matsumoto, K. (1995) · Science · doi:10.1126/science.270.5244.2008 · Cited by 1,343
A mechanism of repression of TGFbeta / Smad signaling by oncogenic Ras
Kretzschmar, M., Doody, J., Timokhina, I., & Massague, J. (1999) · Genes & Development · doi:10.1101/gad.13.7.804 · Cited by 1,004
Human Smad3 and Smad4 Are Sequence-Specific Transcription Activators
Zawel, L., Le Dai, J., Buckhaults, P., Zhou, S., Kinzler, K. W., Vogelstein, B., & Kern, S. E. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80061-1 · Cited by 939
Synergistic Signaling in Fetal Brain by STAT3-Smad1 Complex Bridged by p300
Nakashima, K., Yanagisawa, M., Arakawa, H., Kimura, N., Hisatsune, T., Kawabata, M., Miyazono, K., & Taga, T. (1999) · Science · doi:10.1126/science.284.5413.479 · Cited by 865
TGFβ Signaling: Receptors, Transducers, and Mad Proteins
Massagué, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81296-9 · Cited by 837
Cited by
The transforming growth factor-β superfamily of receptors
de Caestecker, M. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2003.10.004 · Cited by 464
Hayashida, T., de Caestecker, M., & Schnaper, H. W. (2003) · The FASEB Journal · doi:10.1096/fj.03-0037fje · Cited by 361
Self-citationKäkönen, S.-M., Selander, K. S., Chirgwin, J. M., Yin, J. J., Burns, S., Rankin, W. A., Grubbs, B. G., Dallas, M., Cui, Y., & Guise, T. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202561200 · Cited by 276
Li, J. H., Huang, X. R., Zhu, H., Oldfield, M., Cooper, M., Truong, L. D., Johnson, R. J., & Lan, H. Y. (2004) · The FASEB Journal · doi:10.1096/fj.02-1117fje · Cited by 264
TGF-β signaling is required for maintenance of retinal ganglion cell differentiation and survival
Walshe, T. E., Leach, L. L., & D'Amore, P. A. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.05.020 · Cited by 59
Metadata
- Authors
- Watanabe, H., de Caestecker, M. P., & Yamada, Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 276
- Issue
- 17
- Pages
- 14466-14473
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2013515157
- Cited by
- 273
- References
- 58
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Transcriptional Cross-talk between Smad, ERK1/2, and p38 Mitogen-activated Protein Kinase Pathways Regulates Transforming Growth Factor-β-induced Aggrecan Gene Expression in Chondrogenic ATDC5 Cells. https://app.cochat.ai/papers/10.1074/jbc.m005724200
- The paper
- Watanabe, H., de Caestecker, M. P., & Yamada, Y. (2001). Transcriptional Cross-talk between Smad, ERK1/2, and p38 Mitogen-activated Protein Kinase Pathways Regulates Transforming Growth Factor-β-induced Aggrecan Gene Expression in Chondrogenic ATDC5 Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m005724200
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
