Keratin modifications and solubility properties in epithelial cells and in vitro.

M. B. Omary, Nam-on Ku, J. Liao, D. Price

Research output: Contribution to journalReview article

170 Citations (Scopus)

Abstract

The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

Original languageEnglish
Pages (from-to)105-140
Number of pages36
JournalSub-Cellular Biochemistry
Volume31
Publication statusPublished - 1998 Jan 1

Fingerprint

Keratins
Solubility
Epithelial Cells
Phosphorylation
Serine
Apoptosis
In Vitro Techniques
Post Translational Protein Processing
Proteolysis
Glycosylation
Caspases
Type I Keratin
Type II Keratin
Head
Cell signaling
14-3-3 Proteins
Acetylation
Cytoprotection

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology
  • Cancer Research

Cite this

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title = "Keratin modifications and solubility properties in epithelial cells and in vitro.",
abstract = "The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5{\%} of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.",
author = "Omary, {M. B.} and Nam-on Ku and J. Liao and D. Price",
year = "1998",
month = "1",
day = "1",
language = "English",
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pages = "105--140",
journal = "Sub-Cellular Biochemistry",
issn = "0306-0225",
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}

Keratin modifications and solubility properties in epithelial cells and in vitro. / Omary, M. B.; Ku, Nam-on; Liao, J.; Price, D.

In: Sub-Cellular Biochemistry, Vol. 31, 01.01.1998, p. 105-140.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Keratin modifications and solubility properties in epithelial cells and in vitro.

AU - Omary, M. B.

AU - Ku, Nam-on

AU - Liao, J.

AU - Price, D.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

AB - The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

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