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Vol. 14, Issue 11, 4526-4540, November 2003

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Dictyostelium Stress-activated Protein Kinase , a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

Binggang Sun, Hui Ma ^*, and Richard A. Firtel 

Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0634

Submitted January 23, 2003; Revised June 3, 2003; Accepted July 3, 2003
Monitoring Editor: Peter Devreotes

Mitogen-activated protein kinase cascades regulate various cellular functions, including growth, cell differentiation, development, and stress responses. We have identified a new Dictyostelium kinase (stress-activated protein kinase [SAPK]), which is related to members of the mixed lineage kinase class of mitogen-activated protein kinase kinases. SAPK is activated by osmotic stress, heat shock, and detachment from the substratum and by a membrane-permeable cGMP analog, a known regulator of stress responses in Dictyostelium. SAPK is important for cellular resistance to stresses, because SAPK null cells exhibit reduced viability in response to osmotic stress. We found that SAPK mutants affect cellular processes requiring proper regulation of the actin cytoskeleton, including cell motility, morphogenesis, cytokinesis, and cell adhesion. Overexpression of SAPK results in highly elevated basal and chemoattractant-stimulated F-actin levels and strong aggregation and developmental defects, including a failure to polarize and chemotax, and abnormal morphogenesis. These phenotypes require a kinase-active SAPK. SAPK null cells exhibit reduced chemoattractant-stimulated F-actin levels, cytokinesis, developmental and adhesion defects, and a motility defect that is less severe than that exhibited by SAPK-overexpressing cells. SAPK colocalizes with F-actin in F-actin–enriched structures, including membrane ruffles and pseudopodia during chemotaxis. Although SAPK is required for these F-actin–mediated processes, it is not detectably activated in response to chemoattractant stimulation.

Corresponding author. E-mail address: rafirtel{at}ucsd.edu.

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