20962082
not annotated - annotated - LINNAEUS only
The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of the nuclear matrix protein matrin 3.
The protein kinase found in the short region of alphaherpesviruses, termed US3 in herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) and ORF66 in varicella-zoster virus (VZV), affects several viral and host cell processes, and its specific targets remain an area of active investigation. Reports suggesting that HSV-1 US3 substrates overlap with those of cellular protein kinase A (PKA) prompted the use of an antibody specific for phosphorylated PKA substrates to identify US3/ORF66 targets. HSV-1, VZV, and PRV induced very different substrate profiles that were US3/ORF66 kinase dependent. The predominant VZV-phosphorylated 125-kDa species was identified as matrin 3, one of the major nuclear matrix proteins. Matrin 3 was also phosphorylated by HSV-1 and PRV in a US3 kinase-dependent manner and by VZV ORF66 kinase at a novel residue (KRRRT150EE). Since VZV-directed T150 phosphorylation was not blocked by PKA inhibitors and was not induced by PKA activation, and since PKA predominantly targeted matrin 3 S188, it was concluded that phosphorylation by VZV was PKA independent. However, purified VZV ORF66 kinase did not phosphorylate matrin 3 in vitro, suggesting that additional cellular factors were required. In VZV-infected cells in the absence of the ORF66 kinase, matrin 3 displayed intranuclear changes, while matrin 3 showed a pronounced cytoplasmic distribution in late-stage cells infected with US3-negative HSV-1 or PRV. This work identifies phosphorylation of the nuclear matrix protein matrin 3 as a new conserved target of this kinase group.
Ann file
T1 Species 194 221 herpes simplex virus type 1
N1 Reference T1 Taxonomy:10298
T2 Species 223 228 HSV-1
N2 Reference T2 Taxonomy:10298
T3 Species 234 252 pseudorabies virus
N3 Reference T3 Taxonomy:10345
T4 Species 254 257 PRV
N4 Reference T4 Taxonomy:10345
T5 Species 272 294 varicella-zoster virus
N5 Reference T5 Taxonomy:10335
T6 Species 296 299 VZV
N6 Reference T6 Taxonomy:10335
T7 Species 438 443 HSV-1
N7 Reference T7 Taxonomy:10298
T8 Species 619 624 HSV-1
N8 Reference T8 Taxonomy:10298
T9 Species 626 629 VZV
N9 Reference T9 Taxonomy:10335
T10 Species 635 638 PRV
N10 Reference T10 Taxonomy:10345
T11 Species 735 738 VZV
N11 Reference T11 Taxonomy:10335
T12 Species 876 881 HSV-1
N12 Reference T12 Taxonomy:10298
T13 Species 886 889 PRV
N13 Reference T13 Taxonomy:10345
T14 Species 930 933 VZV
N14 Reference T14 Taxonomy:10335
T15 Species 986 989 VZV
N15 Reference T15 Taxonomy:10335
T16 Species 1186 1189 VZV
N16 Reference T16 Taxonomy:10335
T17 Species 1229 1232 VZV
N17 Reference T17 Taxonomy:10335
T18 Species 1349 1352 VZV
N18 Reference T18 Taxonomy:10335
T19 Species 1552 1557 HSV-1
N19 Reference T19 Taxonomy:10298
T20 Species 1561 1564 PRV
N20 Reference T20 Taxonomy:10345