PAK1 kinase is required for CXCL1-induced chemotaxis.

Abstract

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.

• Authors: Dingzhi Wang, Jiging Sai, Glendora Carter, Aristidis Sachpatzidis, Elias Lolis, Ann Richmond
• Journal: Biochemistry (Biochemistry) Vol. 41 Issue 22 Pg. 7100-7 (Jun 04 2002) ISSN: 0006-2960 [Print] United States
• PMID: 12033944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CXCL1 protein, human
• Chemokine CXCL1
• Chemokines, CXC
• Chemotactic Factors
• Cxcl1 protein, rat
• Growth Substances
• Intercellular Signaling Peptides and Proteins
• MAP2K2 protein, human
• Protein-Tyrosine Kinases
• PAK1 protein, human
• Pak1 protein, rat
• Protein Serine-Threonine Kinases
• p21-Activated Kinases
• MAP Kinase Kinase 1
• MAP Kinase Kinase 2
• MAP2K1 protein, human
• Mitogen-Activated Protein Kinase Kinases
• cdc42 GTP-Binding Protein
• Calcium

Topics

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