Cell adhesion differentially regulates the nucleocytoplasmic distribution of active MAP kinases
Cells decide whether to undergo processes, such as proliferation, differentiation and apoptosis, based upon the cues they receive from both circulating factors and integrin-mediated adhesion to the extracellular matrix. Integrins control the activation of the early signaling pathways. For example, g...
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Veröffentlicht in: | Journal of cell science 2002-07, Vol.115 (Pt 13), p.2781-2790 |
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Sprache: | eng |
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Zusammenfassung: | Cells decide whether to undergo processes, such as proliferation, differentiation and apoptosis, based upon the cues they receive from both circulating factors and integrin-mediated adhesion to the extracellular matrix. Integrins control the activation of the early signaling pathways. For example, growth factor activation of the ERK cascade is enhanced when cells are adherent. In addition, adhesion receptors oversee the cellular localization of critical signaling components. We have recently shown that ERK signaling to the nucleus is regulated by cell adhesion at the level of nucleocytoplasmic trafficking. Since the ERKs are only one class of MAP kinase, we extended these studies to include both JNK and p38 MAP kinases. We have rendered JNK and p38 activation in NIH 3T3 fibroblasts anchorage-independent either by treatment with anisomycin or by expression of upstream activators. Under conditions whereby JNK activation is anchorage-independent, we show that localization of JNK to the nucleus and JNK-mediated phosphorylation of c-Jun and Elk-1 is not altered by loss of adhesion. Likewise, the ability of activated p38 to accumulate in the nucleus was similar in suspended and adherent cells. Finally, we show that expression of a form of ERK, which is activated and resistant to nuclear export, reverses the adhesion-dependency of ERK phosphorylation of Elk-1. Thus, adhesion differentially regulates the nucleocytoplasmic distribution of MAP kinase members; ERK accumulation in the nucleus occurs more efficiently in adherent cells, whereas nuclear accumulation of active p38 and active JNK are unaffected by changes in adhesion. |
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ISSN: | 0021-9533 1477-9137 |
DOI: | 10.1242/jcs.115.13.2781 |