Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Growth Differ. 1994 Oct;5(10):1105-17.

Activation of the Axl receptor tyrosine kinase induces mitogenesis and transformation in 32D cells.

Author information

  • 1Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599.

Abstract

axl is a transforming receptor tyrosine kinase isolated from DNA of patients with chronic myelogenous leukemia. Association of axl expression with myelogenous leukemias and its expression in primitive hematopoietic cells suggests a role for axl in myeloid biology. To study the cellular function of axl, we constructed a chimeric receptor tyrosine kinase composed of the extracellular and transmembrane domains of the EGF receptor and the cytoplasmic domain of axl; this chimera was named EAK for EGFR-Axl-Kinase. The EAK chimeric receptor was expressed in the mouse myeloid progenitor cell line 32D, which is dependent on interleukin 3 (IL-3) for proliferation and survival. Treatment of the 32D-EAK cells with EGF stimulated the tyrosine phosphorylation of the axl kinase domain and enabled proliferation through EGF rather than IL-3. Thus, axl can effectively couple with mitogenic signaling pathways intrinsic to 32D myeloid cells. Assay of proteins phosphorylated in response to different cytokine treatments showed that IL-3 and EGF exposure produced unique profiles in the 32D-EAK cells. Furthermore, Jak-2 is phosphorylated only in response to IL-3 treatment in these cells. This suggests that IL-3 receptor and axl transduce mitogenic signals through separate pathways. In addition, exposure of cells expressing the chimeric receptor to EGF for 19 days converted the cells to factor-independent growth, a phenomenon not seen with other receptor tyrosine kinases. Generation of this transformed phenotype is absolutely dependent on axl activation by foster ligand. The tyrosine phosphorylation level of the axl kinase domain in the factor-independent subclones is 40-fold greater than the factor-dependent cells. The association of a unique axl phosphorylation level with the factor-independent phenotype suggests that there is a threshold phosphorylation level of the axl kinase for transformation. The fact that activation of the axl receptor leads to transformation of 32D cells suggests that axl can play a role in leukemic conversion of myeloid cells, either through inappropriate expression or improper activation.

PMID:
7848912
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center