Functional specificity of cytoplasmic and transmembrane tyrosine kinases

Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages

Liliana B. Areces, Persio Dello Sbarba, Manfred Jücker, E. Richard Stanley, Ricardo A. Feldman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF- 1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c- fps/fes did not cause tyrosine phosphorylation or activation of CSF-1- dependent targets, including CSF-1R, She, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross- reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

Original languageEnglish (US)
Pages (from-to)4606-4615
Number of pages10
JournalMolecular and Cellular Biology
Volume14
Issue number7
StatePublished - Jul 1994

Fingerprint

Proto-Oncogene Proteins c-fes
Macrophage Colony-Stimulating Factor
Protein-Tyrosine Kinases
Macrophages
Tyrosine
Phosphorylation
Colony-Stimulating Factor Receptors
Phosphatidylinositol 3-Kinase
Proteins
src Homology Domains
Receptor Protein-Tyrosine Kinases
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Functional specificity of cytoplasmic and transmembrane tyrosine kinases : Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages. / Areces, Liliana B.; Sbarba, Persio Dello; Jücker, Manfred; Stanley, E. Richard; Feldman, Ricardo A.

In: Molecular and Cellular Biology, Vol. 14, No. 7, 07.1994, p. 4606-4615.

Research output: Contribution to journalArticle

Areces, Liliana B. ; Sbarba, Persio Dello ; Jücker, Manfred ; Stanley, E. Richard ; Feldman, Ricardo A. / Functional specificity of cytoplasmic and transmembrane tyrosine kinases : Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages. In: Molecular and Cellular Biology. 1994 ; Vol. 14, No. 7. pp. 4606-4615.
@article{7f4fdbeace17410e924ae93a9411cbc3,
title = "Functional specificity of cytoplasmic and transmembrane tyrosine kinases: Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages",
abstract = "c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF- 1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c- fps/fes did not cause tyrosine phosphorylation or activation of CSF-1- dependent targets, including CSF-1R, She, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross- reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.",
author = "Areces, {Liliana B.} and Sbarba, {Persio Dello} and Manfred J{\"u}cker and Stanley, {E. Richard} and Feldman, {Ricardo A.}",
year = "1994",
month = "7",
language = "English (US)",
volume = "14",
pages = "4606--4615",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Functional specificity of cytoplasmic and transmembrane tyrosine kinases

T2 - Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages

AU - Areces, Liliana B.

AU - Sbarba, Persio Dello

AU - Jücker, Manfred

AU - Stanley, E. Richard

AU - Feldman, Ricardo A.

PY - 1994/7

Y1 - 1994/7

N2 - c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF- 1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c- fps/fes did not cause tyrosine phosphorylation or activation of CSF-1- dependent targets, including CSF-1R, She, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross- reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

AB - c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF- 1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c- fps/fes did not cause tyrosine phosphorylation or activation of CSF-1- dependent targets, including CSF-1R, She, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross- reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

UR - http://www.scopus.com/inward/record.url?scp=0028342640&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028342640&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 4606

EP - 4615

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -