Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.
Rho-associated coiled-coil protein kinase (ROCK) is an effector for the small GTPase Rho and plays a pivotal role in diverse cellular activities, including cell adhesion, cytokinesis, and gene expression, primarily through an alteration of actin cytoskeleton dynamics. Here, we show that ROCK2 is localized in the nucleus and associates with p300 acetyltransferase both in vitro and in cells. Nuclear ROCK2 is present in a large protein complex and partially cofractionates with p300 by gel filtration analysis. By immunofluorescence, ROCK2 partially colocalizes with p300 in distinct insoluble nuclear structures. ROCK2 phosphorylates p300 in vitro, and nuclear-restricted expression of constitutively active ROCK2 induces p300 phosphorylation in cells. p300 acetyltransferase activity is dependent on its phosphorylation status in cells, and p300 phosphorylation by ROCK2 results in an increase in its acetyltransferase activity in vitro. These observations suggest that nucleus-localized ROCK2 targets p300 for phosphorylation to regulate its acetyltransferase activity.
Department of Medicine and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA.
Toru
T
Tanaka
Dai
D
Nishimura
Ray-Chang
RC
Wu
Mutsuki
M
Amano
Tatsuya
T
Iso
Larry
L
Kedes
Hiroshi
H
Nishida
Kozo
K
Kaibuchi
Yasuo
Y
Hamamori
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010449:Peptide Mapping; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D050880:p300-CBP Transcription Factors; D054460:rho-Associated Kinases; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D054460:rho-Associated Kinases; D000099224:p300-CBP-Associated Factor; C515852:ROCK2 protein, human