Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading.
GTPases of the Rho family regulate actinomyosin-based contraction in non-muscle cells. Activation of Rho increases contractility, leading to cell rounding and neurite retraction in neuronal cell lines. Activation of Rac promotes cell spreading and interferes with Rho-mediated cell rounding. Here we show that activation of Rac may antagonize Rho by regulating phosphorylation of the myosin-II heavy chain. Stimulation of PC12 cells or N1E-115 neuroblastoma cells with bradykinin induces phosphorylation of threonine residues in the myosin-II heavy chain; this phosphorylation is Ca2+ dependent and regulated by Rac. Both bradykinin-mediated and constitutive activation of Rac promote cell spreading, accompanied by a loss of cortical myosin II. Our results identify the myosin-II heavy chain as a new target of Rac-regulated kinase pathways, and implicate Rac as a Rho antagonist during myosin-II-dependent cell-shape changes.
van Leeuwen
F N
FN
The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam, The Netherlands.
van Delft
S
S
Kain
H E
HE
van der Kammen
R A
RA
Collard
J G
JG
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D048429:Cell Size / Q000502:physiology; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000205:Actomyosin; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D001920:Bradykinin; D002118:Calcium