Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins

Dwayne L. Barber, Jacqueline M. Mason, Toru Fukazawa, Kris A. Reedquist, Brian J. Druker, Hamid Band, Alan D. D'Andrea

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Transformation of hematopoietic cells by the Bcr-abl oncoprotein leads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine- dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time- dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA- 3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. Of the three Crk isoforms expressed in hematopoietic cells (CrkL, who is Crkll, and Crkl), tyrosine phosphorylated Cbl binds preferentially to CrkL and Crkll. The amount of Cbl associated with CrkL and Crkll exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl- Crk association represents the dominant complex of Cbl in growth factor- stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains. Our data suggest that the inducible Cbl-Crk association is a proximal component of a signaling pathway downstream of multiple cytokine receptors.

Original languageEnglish (US)
Pages (from-to)3166-3174
Number of pages9
JournalBlood
Volume89
Issue number9
StatePublished - May 1 1997

Fingerprint

Phosphorylation
Interleukin-3
Erythropoietin
Tyrosine
Association reactions
Cells
Proteins
Intercellular Signaling Peptides and Proteins
Hematopoietic Cell Growth Factors
Cell Line
Erythroid Cells
Cytokine Receptors
Guanine Nucleotides
src Homology Domains
Oncogene Proteins
Cell proliferation
Protein Isoforms
Cell Proliferation
3-tyrosine
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Barber, D. L., Mason, J. M., Fukazawa, T., Reedquist, K. A., Druker, B. J., Band, H., & D'Andrea, A. D. (1997). Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. Blood, 89(9), 3166-3174.

Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. / Barber, Dwayne L.; Mason, Jacqueline M.; Fukazawa, Toru; Reedquist, Kris A.; Druker, Brian J.; Band, Hamid; D'Andrea, Alan D.

In: Blood, Vol. 89, No. 9, 01.05.1997, p. 3166-3174.

Research output: Contribution to journalArticle

Barber, DL, Mason, JM, Fukazawa, T, Reedquist, KA, Druker, BJ, Band, H & D'Andrea, AD 1997, 'Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins', Blood, vol. 89, no. 9, pp. 3166-3174.
Barber DL, Mason JM, Fukazawa T, Reedquist KA, Druker BJ, Band H et al. Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. Blood. 1997 May 1;89(9):3166-3174.
Barber, Dwayne L. ; Mason, Jacqueline M. ; Fukazawa, Toru ; Reedquist, Kris A. ; Druker, Brian J. ; Band, Hamid ; D'Andrea, Alan D. / Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. In: Blood. 1997 ; Vol. 89, No. 9. pp. 3166-3174.
@article{8c80f5d29bfc48c199ab485e2be1c6df,
title = "Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins",
abstract = "Transformation of hematopoietic cells by the Bcr-abl oncoprotein leads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine- dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time- dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA- 3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. Of the three Crk isoforms expressed in hematopoietic cells (CrkL, who is Crkll, and Crkl), tyrosine phosphorylated Cbl binds preferentially to CrkL and Crkll. The amount of Cbl associated with CrkL and Crkll exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl- Crk association represents the dominant complex of Cbl in growth factor- stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains. Our data suggest that the inducible Cbl-Crk association is a proximal component of a signaling pathway downstream of multiple cytokine receptors.",
author = "Barber, {Dwayne L.} and Mason, {Jacqueline M.} and Toru Fukazawa and Reedquist, {Kris A.} and Druker, {Brian J.} and Hamid Band and D'Andrea, {Alan D.}",
year = "1997",
month = "5",
day = "1",
language = "English (US)",
volume = "89",
pages = "3166--3174",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins

AU - Barber, Dwayne L.

AU - Mason, Jacqueline M.

AU - Fukazawa, Toru

AU - Reedquist, Kris A.

AU - Druker, Brian J.

AU - Band, Hamid

AU - D'Andrea, Alan D.

PY - 1997/5/1

Y1 - 1997/5/1

N2 - Transformation of hematopoietic cells by the Bcr-abl oncoprotein leads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine- dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time- dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA- 3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. Of the three Crk isoforms expressed in hematopoietic cells (CrkL, who is Crkll, and Crkl), tyrosine phosphorylated Cbl binds preferentially to CrkL and Crkll. The amount of Cbl associated with CrkL and Crkll exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl- Crk association represents the dominant complex of Cbl in growth factor- stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains. Our data suggest that the inducible Cbl-Crk association is a proximal component of a signaling pathway downstream of multiple cytokine receptors.

AB - Transformation of hematopoietic cells by the Bcr-abl oncoprotein leads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine- dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time- dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA- 3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. Of the three Crk isoforms expressed in hematopoietic cells (CrkL, who is Crkll, and Crkl), tyrosine phosphorylated Cbl binds preferentially to CrkL and Crkll. The amount of Cbl associated with CrkL and Crkll exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl- Crk association represents the dominant complex of Cbl in growth factor- stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains. Our data suggest that the inducible Cbl-Crk association is a proximal component of a signaling pathway downstream of multiple cytokine receptors.

UR - http://www.scopus.com/inward/record.url?scp=0030969634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030969634&partnerID=8YFLogxK

M3 - Article

C2 - 9129019

AN - SCOPUS:0030969634

VL - 89

SP - 3166

EP - 3174

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -