Calcium signaling regulates translocation and activation of Rac.
Rac is activated in response to various stimuli including growth factors and by adhesion to the extracellular matrix. However, how these stimuli ultimately result in Rac activation is poorly understood. The increase in intracellular calcium [Ca2+]i represents a ubiquitous second messenger system in cells, linking receptor activation to downstream signaling pathways. Here we show that elevation of [Ca2+]i, either artificially or by thrombin receptor activation, potently induces Rac activation. Lamellipodia formation induced by artificial elevation of [Ca2+]i is blocked by inhibition of Rac signaling, indicating that calcium-induced cytoskeletal changes are controlled by the activation of Rac. Calcium-dependent Rac activation was dependent on the activation of a conventional protein kinase C. Furthermore, both increased [Ca2+]i and protein kinase C activation induce phosphorylation of RhoGDI alpha and induce the translocation of cytosolic Rac to the plasma membrane. Intracellular calcium signaling may thus contribute to the intracellular localization and activation of Rac to regulate the cytoskeletal changes in response to receptor stimulation.
Price
Leo S
LS
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
Langeslag
Michiel
M
ten Klooster
Jean Paul
JP
Hordijk
Peter L
PL
Jalink
Kees
K
Collard
John G
JG
D016475:3T3 Cells; D000818:Animals; D001693:Biological Transport, Active; D020013:Calcium Signaling; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D018179:Receptors, Thrombin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
C569638:ARHGDIA protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D018179:Receptors, Thrombin; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D011493:Protein Kinase C; D020744:rac GTP-Binding Proteins