Expression of the activated (Y501-F501) hck tyrosine kinase in 32Dcl3 myeloid cells prolongs survival in the absence of IL-3 and blocks granulocytic differentiation in response to G-CSF.
The hematopoietic cell kinase (hck), a member of the src family of intracellular, membrane-associated protein tyrosine kinases, is primarily expressed in mature granulocytes and monocyte/macrophages. Hck kinase activity plays an essential role in macrophage activation and may be an important signaling molecule in granulocytes. To examine the potential role of hck in hematopoietic differentiation pathways, retroviral vectors were used to express wild-type and mutant forms of p59hck in the hck-negative, interleukin-3 (IL-3) -dependent murine myeloid cell line, 32Dcl3. Constitutive expression of an activated form of hck markedly prolonged the viability of 32Dcl3 cells in the absence of IL-3 but failed to abrogate the requirement for IL-3 for proliferation. Moreover, enforced expression of the activated hck kinase (and less so, the wild-type kinase) blocked granulocytic differentiation of 32Dcl3 cells in response to granulocyte colony-stimulating factor. These findings indicate that up-regulation of hck expression is not required for (and may interfere with) granulocytic differentiation.
English
B K
BK
Crippled Children's Foundation Research Center at Le Bonheur Children's Medical Center, Department of Pediatrics, University of Tennessee, Memphis 38103, USA.
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D004790:Enzyme Induction; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000187:drug effects*; D007377:Interleukin-3 / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051572:Proto-Oncogene Proteins c-hck; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D019061:src-Family Kinases / Q000502:physiology
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases