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p38α MAPK is required for contact inhibition

Abstract

Proliferation of nontransformed cells is regulated by cell–cell contacts, which are referred to as contact-inhibition. Despite its generally accepted importance for cell cycle control, knowledge about the intracellular signalling pathways involved in contact inhibition is scarce. In the present work we show that p38α mitogen-activated protein kinase (MAPK) is involved in the growth-inhibitory signalling cascade of contact inhibition in fibroblasts. p38α activity is increased in confluent cultures of human fibroblasts compared to proliferating cultures. Time course studies show a sustained activation of p38α in response to cell–cell contacts in contrast to a transient activation after serum stimulation. The induction of contact inhibition by addition of glutaraldehyde-fixed cells is impaired by pharmacological inhibition of p38 as well as in p38α−/− fibroblasts. Further evidence for a central role of p38α in contact inhibition comes from the observation that p38α−/− fibroblasts show a higher saturation density compared to wild-type (wt) fibroblasts, which is reversed by reconstituted expression of p38α. In agreement with a defect in contact inhibition, p27Kip1 accumulation is impaired in p38α−/− fibroblasts compared to wt fibroblasts. Hence, our work shows a new role for p38α in contact inhibition and provides a mechanistic basis for the recently proposed tumour suppressive function of this MAPK pathway.

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References

  • Abercrombie M . (1979). Nature, 281, 259–262.

  • Ambrosino C and Nebreda AR . (2001). Biol. Cell, 93, 47–51.

  • Bulavin DV, Demidov O, Saito S, Kauraniemi P, Phillips C, Amundson S, Ambrosino C, Sauter G, Nebreda A, Anderson C, Kallioniemi A, Fornace Jr A and Appella E . (2002). Nat. Genet., 31, 210–215.

  • Bulavin DV, Phillips C, Nannenga B, Timofeev O, Donehower LA, Anderson CW, Appella E and Fornace Jr AJ . (2004). Nat. Genet., 36, 343–350.

  • Casanovas O, Miro F, Estanyol JM, Itarte E, Agel N and Bachs O . (2000). J. Biol. Chem., 275, 35091–35097.

  • Cohen P . (1997). Trends Cell Biol., 7, 353–361.

  • Conrad PW, Rust RT, Han J, Millhorn DE and Beitner-Johnson D . (1999). J. Biol. Chem., 274, 23570–23576.

  • Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher T, Young P and Lee JC . (1995). FEBS Lett., 364, 229–233.

  • Dietrich C, Bartsch T, Schanz F, Oesch F and Wieser R . (1996). Proc. Natl. Acad. Sci. USA, 93, 10815–10819.

  • Dietrich C, Wallenfang K, Oesch F and Wieser F . (1997). Oncogene, 15, 2743–2747.

  • Dulic V, Lees E and Reed SI . (1992). Science, 257, 1958–1961.

  • Eagle H and Levine E . (1967). Nature, 213, 1102–1106.

  • Ellinger-Ziegelbauer H, Kelly K and Siebenlist U . (1999). Mol. Cell. Biol., 19, 3857–3868.

  • Gradl G, Faust D, Oesch F and Wieser R . (1995). Curr. Biol., 5, 526–535.

  • Haq R, Brenton JD, Takahashi M, Finan D, Rottapel R and Zanke B . (2002). Cancer Res., 62, 5076–5082.

  • Heit I, Wieser R, Herget T, Faust D, Borchert-Stuhlträger M, Oesch F and Dietrich C . (2001). Oncogene, 20, 5143–5154.

  • Laemmli UK . (1970). Nature, 227, 680–685.

  • Lavoie JN, L’Allemain G, Brunet A, Müller R and Poussegur J . (1996). J. Biol. Chem., 271, 20608–20616.

  • Molnar A, Theodoras AM, Zon LI and Kyriakis JM . (1997). J. Biol. Chem., 272, 13229–13235.

  • Nakatsuji Y and Miller RH . (1998). Glia, 22, 379–389.

  • Nebreda AR and Porras A . (2000). Trends Biochem. Sci., 25, 257–260.

  • Oesch F, Janik-Schmitt B, Ludewig G, Glatt H-R and Wieser R . (1987). Eur. J. Cell Biol., 43, 403–407.

  • Ono K and Han J . (2000). Cell. Signal., 12, 1–13.

  • Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM and Koff A . (1994). Genes Dev., 8, 9–22.

  • Shi Y and Gaestel M . (2002). Biol. Chem., 383, 1519–1536.

  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ and Klenk DC . (1985). Anal. Biochem., 150, 76–85.

  • Wang XZ and Ron D . (1996). Science, 272, 1347–1349.

  • Wang W, Chen JX, Liao R, Deng Q, Zhou JJ, Huang S and Sun P . (2002). Mol. Cell. Biol., 22, 3389–3403.

  • Wieser R, Heck R and Oesch F . (1985). Exp. Cell Res., 158, 493–499.

  • Wieser R and Oesch F . (1986). J. Cell Biol., 103, 361–367.

  • Wieser R, Schütz S, Tschank G, Dienes H-P, Thomas H and Oesch F . (1990). J. Cell Biol., 111, 2681–2692.

  • Wieser R, Baumann C and Oesch F . (1995). Glycoconjugate J., 12, 672–679.

  • Wieser R, Faust D, Dietrich C and Oesch F . (1999). Oncogene, 18, 277–281.

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Acknowledgements

The expert technical assistance of Sandra Niemann and Emma Black is gratefully acknowledged. This work was supported by the Grant Di 793/1-2 by the Deutsche Forschungsgemeinschaft (CD), by a grant by the Stiftung Rheinland-Pfalz für Innovation (8312-386261/539) and by a grant of the Fundacion Cientifica de la Asociacion Española Contra el Cancer (ARN).

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Correspondence to Cornelia Dietrich.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Faust, D., Dolado, I., Cuadrado, A. et al. p38α MAPK is required for contact inhibition. Oncogene 24, 7941–7945 (2005). https://doi.org/10.1038/sj.onc.1208948

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