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Differentiation and Transforming Growth Factor-β Receptor Down-regulation by Collagen-α2β1 Integrin Interaction Is Mediated by Focal Adhesion Kinase and Its Downstream Signals in Murine Osteoblastic Cells
Open accessAbstract
Interaction of type I collagen (COL(I)) with alpha2beta1 integrin causes differentiation and transforming growth factor (TGF)-beta receptor down-regulation in osteoblastic cells (Takeuchi, Y., Nakayama, K., and Matsumoto, T. (1996) J. Biol. Chem. 271, 3938-3644). The TGF-beta receptor down-regulation enables cells to escape from the inhibition of differentiation by TGF-beta. To clarify how the cell-matrix interaction regulates these phenotypic changes, signaling pathways were examined in murine MC3T3-E1 cells. Attachment of cells to COL(I) stimulated tyrosine phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase (MAPK), and enhanced MAPK activity. Inhibition of tyrosine kinase by herbimycin A, destruction of focal adhesion by cytochalasin D, or overexpression of antisense FAK mRNA prevented the activation of ERK/MAPK and the increase in alkaline phosphatase (ALP) activity. Transient expression of a MAPK-specific phosphatase, CL100, also suppressed the elevation of ALP activity. In addition, introduction of a constitutively active MAPK kinase enhanced ALP activity in the absence of collagen production. TGF-beta receptor down-regulation was abrogated by treatments that inactivate FAK, whereas the expression of CL100 had no effect. These results demonstrate that COL(I)-alpha2beta1 integrin interaction facilitates differentiation and down-regulates TGF-beta receptors via the activation of FAK and its diverse downstream signals. These signaling pathways may play an important role in the sequential differentiation of osteoblasts during bone formation.
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Cites
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase
Schlaepfer, D. D., Hanks, S. K., Hunter, T., & Geer, P. V. D. (1994) · Nature · doi:10.1038/372786a0 · Cited by 1,595
Cited by
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Majidinia, M., Sadeghpour, A., & Yousefi, B. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26042 · Cited by 513
Mizuno, M., Fujisawa, R., & Kuboki, Y. (2000) · Journal of Cellular Physiology · doi:10.1002/1097-4652(200008)184:2<207::aid-jcp8>3.0.co;2-u · Cited by 384
Murphy, A. R., John, P. S., & Kaplan, D. L. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.03.039 · Cited by 277
Walsh, S., Jordan, G. R., Jefferiss, C., Stewart, K., & Beresford, J. N. (2001) · Rheumatology · doi:10.1093/rheumatology/40.1.74 · Cited by 192
Metadata
- Authors
- Takeuchi, Y., Suzawa, M., Kikuchi, T., Nishida, E., Fujita, T., & Matsumoto, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 272
- Issue
- 46
- Pages
- 29309-29316
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1975621622
- Cited by
- 294
- References
- 1
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Differentiation and Transforming Growth Factor-β Receptor Down-regulation by Collagen-α2β1 Integrin Interaction Is Mediated by Focal Adhesion Kinase and Its Downstream Signals in Murine Osteoblastic Cells. https://app.cochat.ai/papers/10.1074/jbc.272.46.29309
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- Takeuchi, Y., Suzawa, M., Kikuchi, T., Nishida, E., Fujita, T., & Matsumoto, T. (1997). Differentiation and Transforming Growth Factor-β Receptor Down-regulation by Collagen-α2β1 Integrin Interaction Is Mediated by Focal Adhesion Kinase and Its Downstream Signals in Murine Osteoblastic Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.46.29309
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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