Abstract
Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism*
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Aspartic Acid / genetics
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Aspartic Acid / metabolism*
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Cell Polarity
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Cells, Cultured
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Chemotaxis*
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Mice
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Mice, Inbred C57BL
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NADPH Oxidases / metabolism
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Neutrophils / cytology*
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Neutrophils / metabolism*
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Protein Transport
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RAC2 GTP-Binding Protein
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Substrate Specificity
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Superoxides / metabolism*
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rac GTP-Binding Proteins / chemistry*
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rac GTP-Binding Proteins / deficiency
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism*
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rac1 GTP-Binding Protein / chemistry
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism
Substances
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Actins
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Superoxides
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Aspartic Acid
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NADPH Oxidases
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein