Nuclear import of protein kinases and cyclins

Boulikas, Teni

doi:10.1002/(sici)1097-4644(19960101)60:1<61::aid-jcb10>3.0.co;2-n

Cited by 24 publications

(13 citation statements)

References 104 publications

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“…The classical monopartite and bipartite NLSs have a tight cluster of basic residues, whereas the three NLSs of 5‐LO consist of dispersed residues. Presuming that the 5‐LO NLSs are bound by importin isoforms to mediate import, it is possible that the arrangement of basic residues may affect the strength of this protein–protein interaction, as has been suggested (24). Alternatively, the residues between the basic amino acids may be important in reducing importin binding and import strength.…”

Section: Resultsmentioning

confidence: 94%

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Luo

Pang

Gerken

et al. 2004

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The nuclear import of proteins typically requires the presence of a nuclear localization sequence (NLS). Some proteins have more than one NLS, but the significance of having multiple NLSs is unclear. The enzyme 5-lipoxygenase (5-LO) has three NLSs that, unlike the tight cluster of basic residues of the classical SV40 large T antigen NLS, contain dispersed basic residues. When attached to green fluorescent protein (GFP), individual 5-LO NLSs caused quantitatively and statistically less import than the SV40 NLS. Combined 5-LO NLSs produced nuclear import that was comparable to that of the SV40 NLS. As expected, GFP/NLS proteins displayed relatively uniform import in all cells. However, a fusion protein of GFP plus the 5-LO protein, modified to contain only one functional NLS, produced some cells with import and some cells without import. A GFP/5-LO fusion protein containing two functional NLSs produced four identifiable levels of nuclear import. Quantitative and visual analysis of a population of cells expressing the intact GFP/5-LO protein, with three intact NLSs, indicated five levels of nuclear import. This suggested that the subcellular distribution of 5-LO may vary widely in normal cells of the body. Consistent with this, immunohistochemical staining of lung sections found that individual macrophages, in situ, displayed cell-specific levels of import of 5-LO. Since nuclear accumulation is known to affect 5-LO activity, multiple NLSs may allow graded regulation of activity via controlled import. Multiple NLSs on other proteins may likewise allow fine control of protein action through modulation of the level of import.

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Section: Resultsmentioning

confidence: 94%

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Luo

Pang

Gerken

et al. 2004

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“…␤ m has no known nuclear localization signals (NLSs); however, ␤ m is very acidic (pI 4.6) and many nuclear proteins possess acidic clusters (7). Strong negative charge is conferred on ␤ m by its NH 2 -terminal domain, a structural feature that distinguishes ␤ m from other ␤-subunits.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of β_m, a structural member of X,K-ATPase β-subunit family, in nuclear envelopes of perinatal myocytes

Zhao

Pestov²,

Korneenko³

et al. 2004

American Journal of Physiology-Cell Physiology

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Zhao, Hao, Nikolay B. Pestov, Tatyana V. Korneenko, Mikhail I. Shakhparonov, and Nikolai N. Modyanov. Accumulation of ␤ m, a structural member of X,K-ATPase ␤-subunit family, in nuclear envelopes of perinatal myocytes. Am J Physiol Cell Physiol 286: C757-C767, 2004. First published December 3, 2003 10.1152/ ajpcell.00358.2003.-Recently discovered muscle-specific ␤ m protein is structurally closely related to the X,K-ATPase ␤-subunits. However, it has a number of unique properties such as predominant localization in intracellular stores and lack of association with known X,K-ATPase ␣-subunits on heterologous coexpression. In this study, the primary structure of mouse ␤ m was determined and developmental regulation of the gene (ATP1B4) was analyzed. The expression is first detected at day 14 of gestation, is sharply increased at day 16, and reaches its maximum at day 18. After birth, the expression quickly decreases and is hardly detectable in adult mice. A more detailed subcellular localization study was undertaken, and its results indicate that ␤ m not only is located in sarcoplasmic reticulum but is concentrated in nuclear envelopes of both prenatal and postnatal skeletal muscles. Immunohistochemical studies show that ␤ m is specific to myocytes and, at the subcellular level, many nuclear envelopes are intensively labeled in both fetal and newborn skeletal muscles. Accordingly, ␤ m is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. On transfection of human rhabdomyosarcoma cell line RD, green fluorescent proteintagged ␤ m resides intracellularly with significant enrichment in nuclear envelopes, whereas ␤ m with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. Nuclear ␤ m apparently is not in association with Na,K-ATPase because we never detected its ␣-subunit in myonuclear membranes. These results indicate that ␤ m has a specialized function in mammalian perinatal myocytes, different from functions of other X,K-ATPase ␤-subunits. The unique temporospatial distribution of ␤ m protein expression suggests its important role in development of growing skeletal muscle.ATP1B4; sodium, potassium-adenosine 5Ј-triphosphatase; nuclear membrane; skeletal muscle development AMONG MORE THAN 200 P-ATPases identified in prokaryotes and eukaryotes (1), most enzymes have just a single catalytic subunit. However, the animal X,K-ATPases (Na,K-ATPase, gastric H,K-ATPase, and nongastric H,K-ATPase) contain, in addition to the catalytic ␣-subunit, an accessory ␤-subunit. Although major functions such as ATP binding, phosphorylation, and ion transport are performed by the ␣-subunit, the ␣-␤ interaction is required for maturation, stability, and translocation of the ATPases to plasma membrane (4, 44). Moreover, the ␤-subunit seems to be related to K transport, the unique feature of the X,K-ATPase family members (16, 45). The ␤-subunit is involved in K affinity and cardiac glycoside sensitivity (25, 45). Different ␣-and ␤-isoform combinations exhibit functiona...

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“…2A), dynamic subnuclear structures that may play a role in transport and/or maturation of small nuclear ribonucleoproteins (snRNPs) [116]. p40 MO15 also contains a strong n6 uclear l6 ocalization s6 ignal (NLS; [117,118]), and mutation of the NLS leads to cytoplasmic localization of inactive p40 MO15 [49,92]. While the nuclear localization of CAK as part of TFIIH may be required for its function, it also agrees with the localization of cdk2, cdk4 and cdk6.…”

Section: Subcellular Localization Of Cakmentioning

confidence: 99%

The cdk-activating kinase (CAK): from yeast to mammals

Kaldis

1999

CMLS, Cell. Mol. Life Sci.

206

188

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Cell cycle progression is regulated by cyclin-dependent kinases (cdks). The activity of cdks is tightly controlled by several mechanisms, including binding of subunits to cdks (cyclins and inhibitors), and phosphorylation events. This review focuses on the activating phosphorylation of cdks by an enzyme termed cdk-activating kinase (CAK). Two classes of CAKs have been identified: monomeric Cak1p from budding yeast and the p40MO15 (cdk7)/cyclin H/MAT1 complex from vertebrates. Cak1p is the physiological CAK in budding yeast and localizes to the cytoplasm. p40MO15(cdk7)/cyclin H/MAT1 localizes to the nucleus, is a subunit of the general transcription factor IIH and activates cdks as well as phosphorylates several components of the transcriptional machinery. Functions, substrate specificities, regulation, localization, effects on cdk structure and involvement in transcription are compared for Cak1p and p40MO15(cdk7).

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Nuclear import of protein kinases and cyclins

Cited by 24 publications

References 104 publications

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Accumulation of β_m, a structural member of X,K-ATPase β-subunit family, in nuclear envelopes of perinatal myocytes

The cdk-activating kinase (CAK): from yeast to mammals

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Nuclear import of protein kinases and cyclins

Cited by 24 publications

References 104 publications

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Multiple Nuclear Localization Sequences Allow Modulation of 5‐Lipoxygenase Nuclear Import

Accumulation of βm, a structural member of X,K-ATPase β-subunit family, in nuclear envelopes of perinatal myocytes

The cdk-activating kinase (CAK): from yeast to mammals

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Accumulation of β_m, a structural member of X,K-ATPase β-subunit family, in nuclear envelopes of perinatal myocytes