Characteristics of the tyrosine recognition signal for internalization of transmembrane surface glycoproteins

Nicholas T. Ktistakis, D'Nette Thomas, Michael G. Roth

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

A tyrosine residue in the cytoplasmic domain of a class of cell surface receptors is necessary, but not sufficient, for internalization through coated pits. To identify the amino acid context enabling a tyrosine to serve as a signal for endocytosis, we mutated the short cytoplasmic domain of a mutant influenza virus hemagglutinin that is competent for internalization, HA-Y543, and determined the effect of each change on internalization. From these results and a comparison of sequences of other proteins recognized by coated pits, a "tyrosine internalization signal" was proposed. Site-directed mutagenesis was employed to insert complete, or incomplete "tyrosine internalization signals" into the cytoplasmic domain of a protein normally not endocytosed, human glycophorin A. Only the complete signal caused internalization of mutant glycophorins by coated pits. The signal is formed by a short amino acid sequence, with polar or basic residues preferred at certain positions on either side of the tyrosine. Amino acids, which in proteins of known structure are frequently found in turns, are clustered near the tyrosine on the side of the signal nearest the transmembrane domain.

Original languageEnglish (US)
Pages (from-to)1393-1407
Number of pages15
JournalJournal of Cell Biology
Volume111
Issue number4
StatePublished - Oct 1990

Fingerprint

Membrane Glycoproteins
Tyrosine
Glycophorin
Endocytosis
Amino Acids
Hemagglutinins
Cell Surface Receptors
Site-Directed Mutagenesis
Orthomyxoviridae
Amino Acid Sequence
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Characteristics of the tyrosine recognition signal for internalization of transmembrane surface glycoproteins. / Ktistakis, Nicholas T.; Thomas, D'Nette; Roth, Michael G.

In: Journal of Cell Biology, Vol. 111, No. 4, 10.1990, p. 1393-1407.

Research output: Contribution to journalArticle

@article{8865e09166c44a0393013b640878d873,
title = "Characteristics of the tyrosine recognition signal for internalization of transmembrane surface glycoproteins",
abstract = "A tyrosine residue in the cytoplasmic domain of a class of cell surface receptors is necessary, but not sufficient, for internalization through coated pits. To identify the amino acid context enabling a tyrosine to serve as a signal for endocytosis, we mutated the short cytoplasmic domain of a mutant influenza virus hemagglutinin that is competent for internalization, HA-Y543, and determined the effect of each change on internalization. From these results and a comparison of sequences of other proteins recognized by coated pits, a {"}tyrosine internalization signal{"} was proposed. Site-directed mutagenesis was employed to insert complete, or incomplete {"}tyrosine internalization signals{"} into the cytoplasmic domain of a protein normally not endocytosed, human glycophorin A. Only the complete signal caused internalization of mutant glycophorins by coated pits. The signal is formed by a short amino acid sequence, with polar or basic residues preferred at certain positions on either side of the tyrosine. Amino acids, which in proteins of known structure are frequently found in turns, are clustered near the tyrosine on the side of the signal nearest the transmembrane domain.",
author = "Ktistakis, {Nicholas T.} and D'Nette Thomas and Roth, {Michael G.}",
year = "1990",
month = "10",
language = "English (US)",
volume = "111",
pages = "1393--1407",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Characteristics of the tyrosine recognition signal for internalization of transmembrane surface glycoproteins

AU - Ktistakis, Nicholas T.

AU - Thomas, D'Nette

AU - Roth, Michael G.

PY - 1990/10

Y1 - 1990/10

N2 - A tyrosine residue in the cytoplasmic domain of a class of cell surface receptors is necessary, but not sufficient, for internalization through coated pits. To identify the amino acid context enabling a tyrosine to serve as a signal for endocytosis, we mutated the short cytoplasmic domain of a mutant influenza virus hemagglutinin that is competent for internalization, HA-Y543, and determined the effect of each change on internalization. From these results and a comparison of sequences of other proteins recognized by coated pits, a "tyrosine internalization signal" was proposed. Site-directed mutagenesis was employed to insert complete, or incomplete "tyrosine internalization signals" into the cytoplasmic domain of a protein normally not endocytosed, human glycophorin A. Only the complete signal caused internalization of mutant glycophorins by coated pits. The signal is formed by a short amino acid sequence, with polar or basic residues preferred at certain positions on either side of the tyrosine. Amino acids, which in proteins of known structure are frequently found in turns, are clustered near the tyrosine on the side of the signal nearest the transmembrane domain.

AB - A tyrosine residue in the cytoplasmic domain of a class of cell surface receptors is necessary, but not sufficient, for internalization through coated pits. To identify the amino acid context enabling a tyrosine to serve as a signal for endocytosis, we mutated the short cytoplasmic domain of a mutant influenza virus hemagglutinin that is competent for internalization, HA-Y543, and determined the effect of each change on internalization. From these results and a comparison of sequences of other proteins recognized by coated pits, a "tyrosine internalization signal" was proposed. Site-directed mutagenesis was employed to insert complete, or incomplete "tyrosine internalization signals" into the cytoplasmic domain of a protein normally not endocytosed, human glycophorin A. Only the complete signal caused internalization of mutant glycophorins by coated pits. The signal is formed by a short amino acid sequence, with polar or basic residues preferred at certain positions on either side of the tyrosine. Amino acids, which in proteins of known structure are frequently found in turns, are clustered near the tyrosine on the side of the signal nearest the transmembrane domain.

UR - http://www.scopus.com/inward/record.url?scp=0025037001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025037001&partnerID=8YFLogxK

M3 - Article

C2 - 2120240

AN - SCOPUS:0025037001

VL - 111

SP - 1393

EP - 1407

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 4

ER -