Intracellular turnover, novel secretion, and mitogenically active intracellular forms of v-sis gene product in simian sarcoma virus-transformed cells

Implications for intracellular loop autocrine transformation

Vinata B Lokeshwar, Shuan Shian Huang, Jung San Huang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In simian sarcoma virus (SSV)-transformed cells (SSV-NRK, SSV-NIH 3T3, and SSV-NP1 cells), the v-sis gene product was synthesized as a 36-kDa glycopolypeptide with one endoglycosidase (Endo) H-sensitive oligosaccharide chain and formed a dimer (p72) with a half-time of <5 min. p72 was proteolytically processed to generate sequentially p68 and p58 in the endoplasmic reticulum/Golgi complex, p44 in the post-Golgi complex compartments, and p27 in an endosomal/lysosomal compartment. A portion (20-30%) of p72 and p68 later became Endo H-resistant but Endo F-sensitive. During processing, the v-sis gene products exhibited rapid turnover, possibly in the endoplasmic reticulum and/or Golgi complex. The rate of turnover correlated with the tumorigenicity previously reported in these SSV-transformed cells. All three SSV-transformed cells secreted v-sis gene product (p44). p44 was secreted but remained tightly associated with the cell surface. This novel secretion provided an efficient system for the interaction of p44 with the cell surface platelet-derived growth factor receptor which resulted in the intracellular formation of p27. A fraction of secreted p44 was converted extracellularly to a 27-kDa product (extracellular p27) after a longer time in culture. The identical N-terminal amino acid sequence of p44 and extracellular p27 (H2N-SLGSLSVAEPAMIA) indicated a preferential site (Lys110-Arg111) for the proteolytic processing. The intracellular turnover of the v-sis gene product and its correlation with tumorigenicity as well as the demonstration of mitogenically active intracellular forms of v-sis gene product support the hypothesis of intracellular loop autocrine transformation.

Original languageEnglish (US)
Pages (from-to)1665-1675
Number of pages11
JournalJournal of Biological Chemistry
Volume265
Issue number3
StatePublished - Jan 25 1990
Externally publishedYes

Fingerprint

Woolly Monkey Sarcoma Virus
sis Genes
Viruses
Genes
Golgi Apparatus
Glycoside Hydrolases
Endoplasmic Reticulum
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Platelet-Derived Growth Factor Receptors
Processing
Oligosaccharides
Dimers
Amino Acid Sequence
Demonstrations
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{c580520c3e95499f8161903e3cea248d,
title = "Intracellular turnover, novel secretion, and mitogenically active intracellular forms of v-sis gene product in simian sarcoma virus-transformed cells: Implications for intracellular loop autocrine transformation",
abstract = "In simian sarcoma virus (SSV)-transformed cells (SSV-NRK, SSV-NIH 3T3, and SSV-NP1 cells), the v-sis gene product was synthesized as a 36-kDa glycopolypeptide with one endoglycosidase (Endo) H-sensitive oligosaccharide chain and formed a dimer (p72) with a half-time of <5 min. p72 was proteolytically processed to generate sequentially p68 and p58 in the endoplasmic reticulum/Golgi complex, p44 in the post-Golgi complex compartments, and p27 in an endosomal/lysosomal compartment. A portion (20-30{\%}) of p72 and p68 later became Endo H-resistant but Endo F-sensitive. During processing, the v-sis gene products exhibited rapid turnover, possibly in the endoplasmic reticulum and/or Golgi complex. The rate of turnover correlated with the tumorigenicity previously reported in these SSV-transformed cells. All three SSV-transformed cells secreted v-sis gene product (p44). p44 was secreted but remained tightly associated with the cell surface. This novel secretion provided an efficient system for the interaction of p44 with the cell surface platelet-derived growth factor receptor which resulted in the intracellular formation of p27. A fraction of secreted p44 was converted extracellularly to a 27-kDa product (extracellular p27) after a longer time in culture. The identical N-terminal amino acid sequence of p44 and extracellular p27 (H2N-SLGSLSVAEPAMIA) indicated a preferential site (Lys110-Arg111) for the proteolytic processing. The intracellular turnover of the v-sis gene product and its correlation with tumorigenicity as well as the demonstration of mitogenically active intracellular forms of v-sis gene product support the hypothesis of intracellular loop autocrine transformation.",
author = "Lokeshwar, {Vinata B} and Huang, {Shuan Shian} and Huang, {Jung San}",
year = "1990",
month = "1",
day = "25",
language = "English (US)",
volume = "265",
pages = "1665--1675",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Intracellular turnover, novel secretion, and mitogenically active intracellular forms of v-sis gene product in simian sarcoma virus-transformed cells

T2 - Implications for intracellular loop autocrine transformation

AU - Lokeshwar, Vinata B

AU - Huang, Shuan Shian

AU - Huang, Jung San

PY - 1990/1/25

Y1 - 1990/1/25

N2 - In simian sarcoma virus (SSV)-transformed cells (SSV-NRK, SSV-NIH 3T3, and SSV-NP1 cells), the v-sis gene product was synthesized as a 36-kDa glycopolypeptide with one endoglycosidase (Endo) H-sensitive oligosaccharide chain and formed a dimer (p72) with a half-time of <5 min. p72 was proteolytically processed to generate sequentially p68 and p58 in the endoplasmic reticulum/Golgi complex, p44 in the post-Golgi complex compartments, and p27 in an endosomal/lysosomal compartment. A portion (20-30%) of p72 and p68 later became Endo H-resistant but Endo F-sensitive. During processing, the v-sis gene products exhibited rapid turnover, possibly in the endoplasmic reticulum and/or Golgi complex. The rate of turnover correlated with the tumorigenicity previously reported in these SSV-transformed cells. All three SSV-transformed cells secreted v-sis gene product (p44). p44 was secreted but remained tightly associated with the cell surface. This novel secretion provided an efficient system for the interaction of p44 with the cell surface platelet-derived growth factor receptor which resulted in the intracellular formation of p27. A fraction of secreted p44 was converted extracellularly to a 27-kDa product (extracellular p27) after a longer time in culture. The identical N-terminal amino acid sequence of p44 and extracellular p27 (H2N-SLGSLSVAEPAMIA) indicated a preferential site (Lys110-Arg111) for the proteolytic processing. The intracellular turnover of the v-sis gene product and its correlation with tumorigenicity as well as the demonstration of mitogenically active intracellular forms of v-sis gene product support the hypothesis of intracellular loop autocrine transformation.

AB - In simian sarcoma virus (SSV)-transformed cells (SSV-NRK, SSV-NIH 3T3, and SSV-NP1 cells), the v-sis gene product was synthesized as a 36-kDa glycopolypeptide with one endoglycosidase (Endo) H-sensitive oligosaccharide chain and formed a dimer (p72) with a half-time of <5 min. p72 was proteolytically processed to generate sequentially p68 and p58 in the endoplasmic reticulum/Golgi complex, p44 in the post-Golgi complex compartments, and p27 in an endosomal/lysosomal compartment. A portion (20-30%) of p72 and p68 later became Endo H-resistant but Endo F-sensitive. During processing, the v-sis gene products exhibited rapid turnover, possibly in the endoplasmic reticulum and/or Golgi complex. The rate of turnover correlated with the tumorigenicity previously reported in these SSV-transformed cells. All three SSV-transformed cells secreted v-sis gene product (p44). p44 was secreted but remained tightly associated with the cell surface. This novel secretion provided an efficient system for the interaction of p44 with the cell surface platelet-derived growth factor receptor which resulted in the intracellular formation of p27. A fraction of secreted p44 was converted extracellularly to a 27-kDa product (extracellular p27) after a longer time in culture. The identical N-terminal amino acid sequence of p44 and extracellular p27 (H2N-SLGSLSVAEPAMIA) indicated a preferential site (Lys110-Arg111) for the proteolytic processing. The intracellular turnover of the v-sis gene product and its correlation with tumorigenicity as well as the demonstration of mitogenically active intracellular forms of v-sis gene product support the hypothesis of intracellular loop autocrine transformation.

UR - http://www.scopus.com/inward/record.url?scp=0025021595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025021595&partnerID=8YFLogxK

M3 - Article

VL - 265

SP - 1665

EP - 1675

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -