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Microfilament assembly is required for anti-IgM dependent MAPK and p90rsk activation in human B lymphocytes
I Melamed1, R A Franklin, E W Gelfand
1Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Abstract:
Mitogen-activated protein kinases (MAPK) are important mediators of signal transduction from the cell surface to the nucleus. These MAPK pathways serve different receptor-mediated signaling pathways leading to dual phosphorylation on serine/threonine and tyrosine residues. The mechanisms linking cytoplasmic MAPK activation to later events is still unclear. In this study we demonstrate that the microfilament system has an active role in MAPK activation. Cross-linking of surface IgM or direct activation of PKC with PMA resulted in time and concentration-dependent increases in F-actin content, MAPK (p42erk-2) activation, and phosphorylation of p90rsk. Pretreatment of the B cells with cytochalasin D or botulinum C2 toxin, microfilament-disrupting agents, prevented the increases in F-actin content as well as MAPK and p90rsk activation. These data indicate a role for the microfilament system in the complex and divergent functions of MAPK.
Insights
The microfilament system actively participates in mitogen-activated protein kinases (MAPK) activation. Disrupting microfilaments blocks key signaling events in B cells, revealing their crucial role in MAPK pathway regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Mitogen-activated protein kinases (MAPK) are crucial signal transducers.
- MAPK pathways regulate diverse cellular processes through phosphorylation.
- The precise mechanisms linking cytoplasmic MAPK activation to downstream events remain incompletely understood.
Purpose of the Study:
- To investigate the role of the microfilament system in MAPK activation.
- To elucidate the involvement of actin cytoskeleton dynamics in B cell signaling.
Main Methods:
- Stimulation of B cells via surface IgM cross-linking or protein kinase C (PKC) activation with phorbol 12-myristate 13-acetate (PMA).
- Assessment of F-actin content, MAPK (p42erk-2) activation, and p90rsk phosphorylation.
- Utilizing microfilament-disrupting agents like cytochalasin D and botulinum C2 toxin.
Main Results:
- Surface IgM cross-linking and PMA treatment induced time- and concentration-dependent increases in F-actin, p42erk-2, and p90rsk.
- Pretreatment with cytochalasin D or botulinum C2 toxin inhibited these increases.
- Microfilament disruption abrogated MAPK and p90rsk activation.
Conclusions:
- The microfilament system plays an active role in mediating MAPK activation in B cells.
- Actin cytoskeleton dynamics are essential for signal transduction through the MAPK pathway.
- These findings highlight the microfilament system's involvement in the complex functions of MAPK.