Selective glucocorticoid control of Rho kinase isoforms regulate cell-cell interactions.
The two Rho kinase isoforms ROCK1 and ROCK2 are downstream effectors of the small GTPase RhoA, although relatively little is known about potential isoform specific functions or the selective control of their cellular activities. Using Con8 rat mammary epithelial cells, we show that the synthetic glucocorticoid dexamethasone strongly stimulates the level of ROCK2 protein, which accounts for the increase in total cellular ROCK2 activity, whereas, steroid treatment down-regulated ROCK1 specific kinase activity without altering ROCK1 protein levels. In Con8 cells, the glucocorticoid induced formation of tight junctions requires the steroid-mediated down-regulation RhoA and function of the RhoA antagonist Rnd3. Treatment with the ROCK inhibitor Y-27632 ablated both the glucocorticoid-induced and Rnd3-mediated stimulation in tight junction sealing. Taken together, our results demonstrate that the expression and activity of ROCK1 and ROCK2 can be uncoupled in a signal-dependent manner, and further implicate a new function for ROCK2 in the steroid control of tight junction dynamics.
Rubenstein
Nicola M
NM
Department of Molecular and Cell Biology, The Cancer Research Laboratory, University of California at Berkeley, 591 LSA, Berkeley, CA 94720-3200, USA.
Callahan
Joseph A
JA
Lo
Daniel H
DH
Firestone
Gary L
GL
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D004790:Enzyme Induction / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000201:enzymology; D054460:rho-Associated Kinases
D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases