BCR/ABL oncogenic tyrosine kinase is responsible for initiating and maintaining the leukeic phenotype of Philadelphia chromosome-positive cells. c-RAF-1 serine/threonine kinase is known to be activated by receptor and nonreceptor tyrosine kinases. To determine whether c-RAF-1 plays a role in the growth of BCR/ABL-dependent cells, we examined whether c-RAF-1 associates with and/or is regulated by BCR/ABL and, if so, whether this interaction is functionally significant for BCR/ABL-dependent growth of chronic myelogenous leukemia cells and for growth factor-dependent proliferation of normal bone marrow cells. We show that c-RAF-1 enzymatic activity is regulated by BCR/ABL, although the protein does not associate with BCR/ABL. Downregulation of c-RAF-1 expression with antisense oligodeoxynucleotides or cDNA constructs, and inhibition of c-RAF-1 activity by its dominant negative mutants, inhibited both BCR/ABL-dependent growth of chronic myelogenous leukemia cells and growth factor-dependent proliferation of normal hematopoietic progenitors and the MO7 cell line without affecting the BCR/ABL-and growth factor-independent proliferation of HL-60 cells. These results indicate that c-RAF-1 plays an important role in Philadelphia chromosome-positive and normal hematopoiesis.

C-RAF-1 serine/threonine kinase is required in BCR/ABL-dependent and normal hematopoiesis / Skorski, T; Nieborowska Skorska, M; Szczylik, C; Kanakaraj, P; Perrotti, D; Zon, G; Gewirtz, A; Perussia, B; Calabretta, Bruno. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 55:(1995), pp. 2275-2278.

C-RAF-1 serine/threonine kinase is required in BCR/ABL-dependent and normal hematopoiesis.

CALABRETTA, Bruno
1995

Abstract

BCR/ABL oncogenic tyrosine kinase is responsible for initiating and maintaining the leukeic phenotype of Philadelphia chromosome-positive cells. c-RAF-1 serine/threonine kinase is known to be activated by receptor and nonreceptor tyrosine kinases. To determine whether c-RAF-1 plays a role in the growth of BCR/ABL-dependent cells, we examined whether c-RAF-1 associates with and/or is regulated by BCR/ABL and, if so, whether this interaction is functionally significant for BCR/ABL-dependent growth of chronic myelogenous leukemia cells and for growth factor-dependent proliferation of normal bone marrow cells. We show that c-RAF-1 enzymatic activity is regulated by BCR/ABL, although the protein does not associate with BCR/ABL. Downregulation of c-RAF-1 expression with antisense oligodeoxynucleotides or cDNA constructs, and inhibition of c-RAF-1 activity by its dominant negative mutants, inhibited both BCR/ABL-dependent growth of chronic myelogenous leukemia cells and growth factor-dependent proliferation of normal hematopoietic progenitors and the MO7 cell line without affecting the BCR/ABL-and growth factor-independent proliferation of HL-60 cells. These results indicate that c-RAF-1 plays an important role in Philadelphia chromosome-positive and normal hematopoiesis.
1995
55
2275
2278
C-RAF-1 serine/threonine kinase is required in BCR/ABL-dependent and normal hematopoiesis / Skorski, T; Nieborowska Skorska, M; Szczylik, C; Kanakaraj, P; Perrotti, D; Zon, G; Gewirtz, A; Perussia, B; Calabretta, Bruno. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 55:(1995), pp. 2275-2278.
Skorski, T; Nieborowska Skorska, M; Szczylik, C; Kanakaraj, P; Perrotti, D; Zon, G; Gewirtz, A; Perussia, B; Calabretta, Bruno
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/812295
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 66
  • ???jsp.display-item.citation.isi??? 63
social impact