Lamin B is rapidly phosphorylated in lymphocytes after activation of protein kinase C.

Hornbeck, Peter; Huang, Kuo‐Ping; Paul, William E.

doi:10.1073/pnas.85.7.2279

Cited by 86 publications

(30 citation statements)

References 27 publications

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“…The inner surface of the nuclear membrane is lined with a meshwork of protein called the nuclear lamina, a function of which may be mechanical support (21,22). A major component of lymphocyte nuclear lamina is the type V IF protein lamin B (23). Although the lamin B nucleoskeleton can be disassembled by serine phosphorylation (24), this does not occur in lymphocytes during the calyculin A treatment that we used to disassemble vimentin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Rigidity of Circulating Lymphocytes Is Primarily Conferred by Vimentin Intermediate Filaments

Brown

Hallam

Colucci‐Guyon

et al. 2001

The Journal of Immunology

141

115

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Lymphocytes need rigidity while in circulation, but must abruptly become deformable to undergo transmigration into tissue. Previously, the control of leukocyte deformability has been attributed to microfilaments or microtubules, but the present studies demonstrate the greater importance of vimentin intermediate filaments (IFs). In circulating T lymphocytes, IFs form a distinctive spherical cage that undergoes a rapid condensation into a juxtanuclear aggregate during chemokine-induced polarization. Measurements of the resistance of peripheral blood T lymphocytes to global deformation demonstrate that their rigidity is primarily dependent on intact vimentin filaments. Microtubules, in contrast, are not sufficient to maintain rigidity. Thus, vimentin IFs are a primary source of structural support in circulating human lymphocytes, and their regulated collapse is likely to be an essential element in chemokine-induced transendothelial migration.

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Section: Resultsmentioning

confidence: 99%

Rigidity of Circulating Lymphocytes Is Primarily Conferred by Vimentin Intermediate Filaments

Brown

Hallam

Colucci‐Guyon

et al. 2001

The Journal of Immunology

141

115

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“…Mitotic disassembly and reassembly of the lamina is regulated by reversible lamin phosphorylation and dephosphorylation (1). Interphase lamin phosphorylation has also been reported (2)(3)(4)(5)(6), but its significance is not fully understood.…”

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confidence: 99%

“…They include cyclin B/p34 cdc2 (7), S6 kinase II (8), protein kinase C (PKC) (4,9), and the cAMP-dependent protein kinase PKA (10). Down-regulation of PKA has also been shown to be essential for mitotic lamina disassembly (11).…”

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confidence: 99%

Protein Kinase C-mediated Interphase Lamin B Phosphorylation and Solubilization

Collas¹,

Thompson²,

Fields³

et al. 1997

Journal of Biological Chemistry

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Disassembly of the sperm nuclear envelope at fertilization is one of the earliest events in the development of the male pronucleus. We report that nuclear lamina disassembly in interphase sea urchin egg cytosol is a result of lamin B phosphorylation mediated by protein kinase C (PKC). Lamin B of permeabilized sea urchin sperm nuclei incubated in fertilized egg G 1 phase cytosolic extract is phosphorylated within 1 min of incubation and solubilized prior to sperm chromatin decondensation. Phosphorylation is Ca 2؉ -dependent. It is reversibly inhibited by the PKC-specific inhibitor chelerythrine, a PKC pseudosubstrate inhibitor peptide, and a PKC substrate peptide, but not by inhibitors of PKA, p34 cdc2 or calmodulin kinase II. Phosphorylation is inhibited by immunodepletion of cytosolic PKC and restored by addition of purified rat brain PKC. Sperm lamin B is a substrate for rat brain PKC in vitro, resulting in lamin B solubilization. Two-dimensional phosphopeptide maps of lamin B phosphorylated by the cytosolic kinase and by purified rat PKC are virtually identical. These data suggest that PKC is the major kinase required for interphase disassembly of the sperm lamina.The nuclear lamina consists of a polymeric network of intermediate filament molecules, the nuclear lamins, underlying the inner nuclear membrane. The lamina is a dynamic structure, undergoing expansion during interphase of the cell cycle, and depolymerization at mitosis upon breakdown of the nuclear envelope (NE) 1 (1). Mitotic disassembly and reassembly of the lamina is regulated by reversible lamin phosphorylation and dephosphorylation (1). Interphase lamin phosphorylation has also been reported (2-6), but its significance is not fully understood.Several lamin kinases have been identified that promote mitotic lamina solubilization or inhibit lamina assembly in vitro. They include cyclin B/p34 cdc2 (7), S6 kinase II (8), protein kinase C (PKC) (4, 9), and the cAMP-dependent protein kinase PKA (10). Down-regulation of PKA has also been shown to be essential for mitotic lamina disassembly (11). Although not a lamin kinase, Ca 2ϩ /calmodulin-dependent kinase II (CaM kinase II) is also involved in mitotic NE breakdown in sea urchin embryos (12). PKC has also been shown to phosphorylate chicken lamin B 2 in interphase, a process thought to regulate lamin import into the nucleus (13). These observations imply that multiple kinases regulate the dynamics of the nuclear lamina during the cell cycle. The transformation of the sea urchin sperm nucleus into a pronucleus at fertilization provides an opportunity to investigate NE assembly/disassembly during interphase. Sea urchin eggs are fertilized in G 1 phase of the first cell cycle after completion of both meiotic divisions. At fertilization, the sperm NE vesiculates and a new NE reforms around the male pronucleus as the sperm chromatin decondenses (14). Male pronuclear formation has been duplicated in a cell-free system by incubating detergent-permeabilized sperm nuclei in fertilized egg extracts (15)(16)(1...

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“…PMC, formerly known as protein 5 (16,17), appears to be identical with the widely studied 80-to 87-kilodalton (kDa) PKC substrate in neural tissue (2,38) and fibroblasts (5,43,46). The phosphorylation of PMC increases immediately after activation of PKC in lymphocytes (16), fibroblasts (43), and synaptosomes (26) and is stimulated by a number of physiological ligands (2,5,17,22,43,46), as well as phorbol esters, potent pharmacological activators of PKC (34). The strength of the correlation between the phosphorylation of PMC and the physiological activation of PKC argues that PMC is an important mediator of PKC activity (2).…”

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confidence: 99%

A major myristylated substrate of protein kinase C and protein kinase C itself are differentially regulated during murine B- and T-lymphocyte development and activation.

Hornbeck¹,

Nakabayashi²,

Fowlkes³

et al. 1989

Mol. Cell. Biol.

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The regulation and expression of protein kinase C (PKC) and phosphomyristin C (PMC) (a principal substrate of PKC which is the major myristylated protein in lymphocyte and glioma lines that express it) in murine B and T lymphocytes were investigated. Both PMC and PKC are differentially regulated during T-cell development. The level of PMC expression is highest in CD4-8-, intermediate in CD4+8+, and lowest in Jlld-, CD4, or CD8 single-positive thymocytes. PKC is equally expressed by all three thymic populations. In striking contrast to thymocytes, resting peripheral lymph node T cells and T-cell clones express little if any PMC and reduced levels of PKC. Neither PKC nor PMC is signfficantly induced upon the activation of lymph node T cells: treatment with anti-CD3 antibodies or anti-CD3 and interleukin-2 fails to induce PKC, whereas PMC is not induced by anti-CD3 alone and is only slightly induced by anti-CD3 and interleukin-2. In contrast to the situation with T cells, PMC and PKC are constitutively expressed at moderate levels in mature B cells. PMC is greatly increased in B-cell blasts generated by cross-linking the antigen receptor with antiimmunoglobulin. These results demonstrate that PMC and PKC are differentially regulated during the development and activation of B and T cells, suggesting that cellular events that rely upon PKC and PMC may differ during ontogeny and activation of different lymphocyte subsets.

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Lamin B is rapidly phosphorylated in lymphocytes after activation of protein kinase C.

Cited by 86 publications

References 27 publications

Rigidity of Circulating Lymphocytes Is Primarily Conferred by Vimentin Intermediate Filaments

Rigidity of Circulating Lymphocytes Is Primarily Conferred by Vimentin Intermediate Filaments

Protein Kinase C-mediated Interphase Lamin B Phosphorylation and Solubilization

A major myristylated substrate of protein kinase C and protein kinase C itself are differentially regulated during murine B- and T-lymphocyte development and activation.

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