Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells.
Mast cells generated from Rac2-deficient (-/-) mice demonstrated defective actin-based functions, including adhesion, migration, and degranulation. Rac2(-/-) mast cells generated lower numbers and less mast cell colonies in response to growth factors and were deficient in vivo. Rac2(-/-) mast cells demonstrated a significant reduction in growth factor-induced survival, which correlated with the lack of activation of Akt and significant changes in the expression of the Bcl-2 family members BAD and Bcl-XL, in spite of a 3-fold induction of Rac1 protein. These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor-dependent survival and expression of BAD/Bcl-XL.
Yang
F C
FC
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA.
Kapur
R
R
King
A J
AJ
Tao
W
W
Kim
C
C
Borneo
J
J
Breese
R
R
Marshall
M
M
Dinauer
M C
MC
Williams
D A
DA
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D051025:bcl-Associated Death Protein; D020744:rac GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D000097766:RAC2 GTP-Binding Protein
D000199:Actins; D002352:Carrier Proteins; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C494820:Bad protein, mouse