The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization.
Rac GTPases regulate a wide variety of cellular processes including actin cytoskeleton organization, gene expression, cell-cycle progression, and apoptosis. Here we report that the TRQQKRP motif of Rac2 located near the C-terminus, a region of sequence disparity among Rac proteins, is essential for complementation of Rac2 function in Rac2-deficient cells. Deletion of this sequence can also intragenically suppress the dominant-negative Rac2(D57N) mutation in a variety of functional assays. In Rac2-deficient cells, expression of TRQQKRP-deleted Rac2 protein is unable to completely rescue migration and nicotinamide adenine dinucleotide phosphate oxidase deficiencies previously described in these cells. In fibroblasts, the Rac2(D57N) mutant phenotypes of abnormal proliferation, cell morphology, and membrane ruffling are suppressed by the TRQQKRP motif deletion. In myeloid hematopoietic cells, the deletion of the TRQQKRP motif eliminates a Rac2(D57N)-induced block in in vitro differentiation of neutrophils not previously described with this mutant. Mechanistically, deletion of the TRQQKRP motif results in diminished geranylgeranylation and delocalization of intracellular Rac2 protein. Taken together, these results indicate that the TRQQKRP motif in Rac2 protein is required for efficient prenylation and correct intracellular localization of Rac2 protein and is essential for Rac2 to mediate a variety of its biologic functions. These data suggest that precise localization of Rac2 protein in intracellular compartments and/or with other proteins/lipids is a prerequisite for its diverse functions.
Tao
Wen
W
Howard Hughes Medical Institute, USA.
Filippi
Marie-Dominique
MD
Bailey
Jeffrey R
JR
Atkinson
Simon J
SJ
Connors
Bret
B
Evan
Andrew
A
Williams
David A
DA
D016475:3T3 Cells; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*; D000097766:RAC2 GTP-Binding Protein
D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein