Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: Potential relevance to neoplastic lymphohematopoietic cells

Anne Astier, Serge N. Manié, Susan F. Law, Timothy Canty, Nilou Haghayghi, Brian Druker, Ravi Salgia, Erica A. Golemis, Arnold S. Freedman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

CrkL, a cellular homologue of the v-crk oncogene, belongs to the family of adaptor proteins, containing SH2 and SH3 domains, but no catalytic domain. Stimulation of normal B-cells and B-cell lines through β1 integrin or - cell antigen receptor (BCR) promoted the association of CrkL with a set of 105-130 kD tyrosine phosphorylated substrates. The principal substrate is a recently identified molecule known as p105(HEF1) (HEF1), which is highly homologous to p130(Cas) (Cas), the major tyrosine-phosphorylated protein detected in fibroblasts after transformation by v-crk. Immunodepletion studies indicated that all the tyrosine phosphorylated HEF1 or Cas was complexed with CrkL. Furthermore, the guanine nucleotide exchange factor C3G, which is thought to be involved in the regulation of the ras pathway and constituvely binds to the C-terminal SH3 domain of CrkL, could be detected in HEF1 immunoprecipitates. Therefore, CrkL is involved in the formation of a HEF1-CrkL-C3G ternary complex in B-cells, suggesting that it is likely to play an important role, allowing the propagation of the stimulation initiated by both BCR and β1 integrin ligation.

Original languageEnglish (US)
Pages (from-to)65-72
Number of pages8
JournalLeukemia and Lymphoma
Volume28
Issue number1-2
StatePublished - 1997

Fingerprint

Antigen Receptors
src Homology Domains
Integrins
Tyrosine
B-Lymphocytes
Guanine Nucleotide-Releasing Factor 2
Oncogenes
Ligation
Catalytic Domain
Proteins
Fibroblasts
Cell Line

Keywords

  • Antigen receptor signaling human B-cells
  • B-cell
  • B-cell antigen receptor
  • Cas
  • Cas-like molecule
  • CrkL
  • HEF1
  • Integrins

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells : Potential relevance to neoplastic lymphohematopoietic cells. / Astier, Anne; Manié, Serge N.; Law, Susan F.; Canty, Timothy; Haghayghi, Nilou; Druker, Brian; Salgia, Ravi; Golemis, Erica A.; Freedman, Arnold S.

In: Leukemia and Lymphoma, Vol. 28, No. 1-2, 1997, p. 65-72.

Research output: Contribution to journalArticle

Astier, Anne ; Manié, Serge N. ; Law, Susan F. ; Canty, Timothy ; Haghayghi, Nilou ; Druker, Brian ; Salgia, Ravi ; Golemis, Erica A. ; Freedman, Arnold S. / Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells : Potential relevance to neoplastic lymphohematopoietic cells. In: Leukemia and Lymphoma. 1997 ; Vol. 28, No. 1-2. pp. 65-72.
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abstract = "CrkL, a cellular homologue of the v-crk oncogene, belongs to the family of adaptor proteins, containing SH2 and SH3 domains, but no catalytic domain. Stimulation of normal B-cells and B-cell lines through β1 integrin or - cell antigen receptor (BCR) promoted the association of CrkL with a set of 105-130 kD tyrosine phosphorylated substrates. The principal substrate is a recently identified molecule known as p105(HEF1) (HEF1), which is highly homologous to p130(Cas) (Cas), the major tyrosine-phosphorylated protein detected in fibroblasts after transformation by v-crk. Immunodepletion studies indicated that all the tyrosine phosphorylated HEF1 or Cas was complexed with CrkL. Furthermore, the guanine nucleotide exchange factor C3G, which is thought to be involved in the regulation of the ras pathway and constituvely binds to the C-terminal SH3 domain of CrkL, could be detected in HEF1 immunoprecipitates. Therefore, CrkL is involved in the formation of a HEF1-CrkL-C3G ternary complex in B-cells, suggesting that it is likely to play an important role, allowing the propagation of the stimulation initiated by both BCR and β1 integrin ligation.",
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AU - Canty, Timothy

AU - Haghayghi, Nilou

AU - Druker, Brian

AU - Salgia, Ravi

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AU - Freedman, Arnold S.

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