Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27
Open Access
- 1 February 1997
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 110 (3), 357-368
- https://doi.org/10.1242/jcs.110.3.357
Abstract
We have studied the contribution of the individual kinases of the MAP (mitogen-activated protein) kinase family, including ERK (extracellular-signal regulated kinase), JNK/SAPK (c-JUN NH2-terminal kinase/stress-activated protein kinase) and p38, to activation of the HSP27 (heat shock protein 27) kinase MAPKAP kinase-2/3 and to HSP27 phosphorylation in Chinese hamster CCL39 cells stimulated by either growth factors, cytokines or stressing agents. In vitro assays using fractionated cell extracts or immunoprecipitates indicated that only fractions containing ERK or p38, and not those containing JNK/SAPK, had the capacity to activate MAPKAP kinase-2/3. In vivo, however, it appeared that only p38 is an upstream activator of HSP27 phosphorylation after both stress or growth factor stimulation: expression of an interfering mutant of ras, which blocked the activation of ERK by both types of inducers, had no effect on HSP27 phosphorylation and p38 activation; and the cell-permeant specific inhibitor of 038, SB203580, blocked MAPKAP-kinase2/3 activation and HSP27 phosphorylation. HSP27 has been suggested to have a phosphorylation-activated homeostatic function at the actin cytoskeleton level. This raises the possibility that p38 might be directly involved in mediating actin responses to external stimuli. Accordingly, we observed that a prior activation of p38 increased the stability of the actin microfilaments in cells exposed to cytochalasin D. The effect was dependent on the expression of HSP27 and was totally annihilated by blocking the p38 activity with SB203580. The results provide strong support to the idea that activation of p38 during adverse environmental conditions serves a homeostatic function aimed at regulating actin dynamics that would otherwise be destabilized during stress. Its activation during normal agonist stimulation may constitute an additional actin signaling pathway, the importance of which depends on the level of expression of HSP27.Keywords
This publication has 62 references indexed in Scilit:
- Rho Family GTPases Regulate p38 Mitogen-activated Protein Kinase through the Downstream Mediator Pak1Journal of Biological Chemistry, 1995
- SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1FEBS Letters, 1995
- Characterization of 45‐kDa/54‐kDa HSP27 Kinase, a Stress‐Sensitive Kinase Which may Activate the Phosphorylation‐Dependent Protective Function of Mammalian 27‐kDa Heat‐shock Protein HSP27European Journal of Biochemistry, 1995
- MAPKs: new JNK expands the groupTrends in Biochemical Sciences, 1994
- Small GTP-Binding Proteins and the Regulation of the Actin CytoskeletonAnnual Review of Cell Biology, 1994
- Transformation of Mammalian Cells by Constitutively Active MAP Kinase KinaseScience, 1994
- A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian CellsScience, 1994
- MAP kinase activation during heat shock in quiescent and exponentially growing mammalian cellsFEBS Letters, 1993
- Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteinsFEBS Letters, 1992
- The role of solation-contraction coupling in regulating stress fiber dynamics in nonmuscle cells.The Journal of cell biology, 1991