PAK1 kinase is required for CXCL1-induced chemotaxis.

Wang D, Sai J, Carter G, Sachpatzidis A, Lolis E, Richmond A
Biochemistry. 2002 41 (22): 7100-7

PMID: 12033944 · PMCID: PMC2668253 · DOI:10.1021/bi025902m

The CXC subfamily of chemokines plays an important role in diverse processes, including inflammation, wound healing, growth regulation, angiogenesis, and tumorigenesis. The CXC chemokine CXCL1, or MGSA/GROalpha, is traditionally considered to be responsible for attracting leukocytes into sites of inflammation. To better understand the molecular mechanisms by which CXCL1 induces CXCR2-mediated chemotaxis, the signal transduction components involved in CXCL1-induced chemotaxis were examined. It is shown here that CXCL1 induces cdc42 and PAK1 activation in CXCR2-expressing HEK293 cells. Activation of the cdc42-PAK1 cascade is required for CXCL1-induced chemotaxis but not for CXCL1-induced intracellular Ca2+ mobilization. Moreover, CXCL1 activation of PAK1 is independent of ERK1/2 activation, a conclusion based on the observations that the inhibition of MEK-ERK activation by expression of dominant negative ERK or by the MEK inhibitor, PD98059, has no effect on CXCL1-induced PAK1 activation or CXCL1-induced chemotaxis.

MeSH Terms (21)

Animals Calcium cdc42 GTP-Binding Protein Cell Line Chemokine CXCL1 Chemokines, CXC Chemotactic Factors Chemotaxis Enzyme Activation Growth Substances Humans Intercellular Signaling Peptides and Proteins MAP Kinase Kinase 1 MAP Kinase Kinase 2 Mitogen-Activated Protein Kinase Kinases p21-Activated Kinases Protein-Serine-Threonine Kinases Protein-Tyrosine Kinases Rats Signal Transduction Tumor Cells, Cultured

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