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Verdecia, Mark A.; Bowman, M.E.; Lu, Kun Ping; Hunter, Tony; Noel, Joseph P.

doi:10.1038/77929

Cited by 660 publications

(389 citation statements)

References 31 publications

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“…Molecular mass standards are shown on the left. All data shown in this figure are representative of at least three independent experiments containing proline residues and phosphorylated serines (Verdecia et al, 2000). The association of some phosphoproteins with Pin1 has been found to regulate their rate of dephosphorylation, perhaps through Pin1-induced conformational changes that alter the accessibility of phosphorylated residues to phosphatases (Lu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

et al. 2003

Oncogene

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Disabled-2 (Dab2; also known as p96 and DOC-2) is a signal transduction protein that has been implicated in the control of cell growth. Dab2 is known to be a phosphoprotein, but little is known about the kinases that phosphorylate Dab2. We have found that Dab2 phosphorylation is markedly increased during the mitosis phase of the cell cycle. This phosphorylation is blocked by roscovitine, a selective inhibitor of cyclin-dependent kinases. Dab2 robustly coimmunoprecipitates from cells with the cyclin-dependent kinase cdc2, and purified cdc2 can phosphorylate purified Dab2 fusion proteins in vitro on multiple sites. Cellular phosphorylation of Dab2 by cdc2 promotes the association of Dab2 with Pin1, a peptidylprolyl isomerase that regulates the rate of Dab2 dephosphorylation. These findings reveal that Dab2 is differentially phosphorylated during the cell cycle by cdc2 and provide a potential feedback mechanism by which Dab2 inhibition of cell growth and proliferation may be regulated.

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Section: Discussionmentioning

confidence: 99%

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

et al. 2003

Oncogene

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“…The hydrophobic grooves are formed by a conserved set of three aromatic residues, Tyr͞Phe, Tyr͞Phe, and Trp, which are arranged approximately linearly on the molecular surface. Similarly, WW domains, which also bind to PPII helices, have two conserved aromatics that form one X-P binding groove, emphasizing the importance of these grooves in PPII helix recognition (30,31). In MIA, four of six of the conserved SH3 binding site residues differ from canonical SH3 domains (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins

Lougheed

Holton

Alber

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Melanoma inhibitory activity (MIA) is a 12-kDa protein that is secreted from both chondrocytes and malignant melanoma cells. MIA has been reported to have effects on cell growth and adhesion, and it may play a role in melanoma metastasis and cartilage development. We report the 1.4-Å crystal structure of human MIA, which consists of an Src homology 3 (SH3)-like domain with N-and C-terminal extensions of about 20 aa each. The N-and C-terminal extensions add additional structural elements to the SH3 domain, forming a previously undescribed fold. MIA is a representative of a recently identified family of proteins and is the first structure of a secreted protein with an SH3 subdomain. The structure also suggests a likely protein interaction site and suggests that, unlike conventional SH3 domains, MIA does not recognize polyproline helices.

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“…The structure of lamin A in complex with Pin1 was modeled based on the known crystal structure of Pin1 in complex with a peptide from the RNA polymerase II C-terminal domain (Protein Data Bank code 1f8a) (35). For this purpose, the C-terminal domain ligand sequence was replaced with that of lamin A using the lowest energy rotamers for the non-conserved amino acid side chains.…”

Section: Indirect Immunofluorescence Double Staining and Confocal Lasmentioning

confidence: 99%

Novel Mode of Phosphorylation-triggered Reorganization of the Nuclear Lamina during Nuclear Egress of Human Cytomegalovirus

Milbradt

Webel

Auerochs

et al. 2010

Journal of Biological Chemistry

148

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The nucleocytoplasmic egress of viral capsids is a rate-limiting step in the replication of the human cytomegalovirus (HCMV). As reported recently, an HCMV-specific nuclear egress complex is composed of viral and cellular proteins, in particular protein kinases with the capacity to induce destabilization of the nuclear lamina. Viral protein kinase pUL97 and cellular protein kinase C (PKC) play important roles by phosphorylating several types of nuclear lamins. Using pUL97 mutants, we show that the lamin-phosphorylating activity of pUL97 is associated with a reorganization of nuclear lamin A/C. Either pUL97 or PKC has the potential to induce distinct punctate lamina-depleted areas at the periphery of the nuclear envelope, which were detectable in transiently transfected and HCMV-infected cells. Using recombinant HCMV, which produces green fluorescent protein-labeled viral capsids, the direct transition of viral capsids through these areas could be visualized. This process was sensitive to an inhibitor of pUL97/PKC activity. The pUL97-mediated phosphorylation of lamin A/C at Ser 22 generated a novel binding motif for the peptidyl-prolyl cis/trans-isomerase Pin1. In HCMV-infected fibroblasts, the physiological localization of Pin1 was altered, leading to recruitment of Pin1 to viral replication centers and to the nuclear lamina. The local increase in Pin1 peptidyl-prolyl cis/trans-isomerase activity may promote conformational modulation of lamins. Thus, we postulate a novel phosphorylation-triggered mechanism for the reorganization of the nuclear lamina in HCMVinfected cells. Human cytomegalovirus (HCMV)2 belongs to the ␤-herpesvirus subfamily, exhibiting worldwide distribution. When infecting immunocompetent individuals, HCMV possesses low pathogenicity, causing mainly asymptomatic infections. In immunocompromised or immunosuppressed hosts, HCMV infection can cause severe and even life-threatening diseases, including pneumonitis, retinitis, hepatitis, encephalitis, and gastroenteritis (1-3).HCMV replication is based on a nuclear phase, a characteristic of most DNA viruses. Transition from the nuclear to the cytoplasmic phase is determined by the nuclear exit of DNAfilled capsids budding through the inner nuclear membrane (INM) (4 -6). The site-specific budding of viral capsids through distinct locally occurring invaginations in the INM of HCMVinfected cells was clearly illustrated by Buser et al. (7) using electron microscopic analysis. The proteinaceous network of the nuclear lamina, underlying the INM, constitutes a major obstacle for the nuclear egress of capsids. Lamins, belonging to type V intermediate filament proteins, are the main constituents of the nuclear lamina and are grouped into A and B types. A-type lamins (A, C, A⌬10, and C2; collectively lamin A/C) result from alternative splicing of the LMNA gene. B-type lamins are encoded by the LMNB1 (B1) or LMNB2 (B2, B3) gene (8, 9). A major function of the nuclear lamina is to maintain the structure of the nuclear envelope. During mitosis, the nuclear lamin...

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Untitled

Cited by 660 publications

References 31 publications

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins

Novel Mode of Phosphorylation-triggered Reorganization of the Nuclear Lamina during Nuclear Egress of Human Cytomegalovirus

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