Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase

Y. Sawada, K. Nakamura, K. Doi, K. Takeda, K. Tobiume, M. Saitoh, K. Morita, I. Komuro, K. De Vos, M. Sheetz, H. Ichijo

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.

Original languageEnglish (US)
Pages (from-to)1221-1227
Number of pages7
JournalJournal of Cell Science
Volume114
Issue number6
StatePublished - Apr 23 2001

Keywords

  • MAP kinase cascade
  • Mechanical stress
  • Rap1
  • Ras
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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    Sawada, Y., Nakamura, K., Doi, K., Takeda, K., Tobiume, K., Saitoh, M., Morita, K., Komuro, I., De Vos, K., Sheetz, M., & Ichijo, H. (2001). Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase. Journal of Cell Science, 114(6), 1221-1227.