Src kinases in G-CSF receptor signaling.
The Granulocyte Colony-Stimulating Factor (G-CSF) receptor, a member of the hematopoietin cytokine receptor superfamily, functions as a homodimer and requires the recruitment of cytosolic protein tyrosine kinases (PTKs) to transduce its signal. At least two cytosolic PTKs are primarily involved: Jak2, a member of the Janus family, and Lyn, a member of the Src family. Through poorly understood mechanisms, these kinases functionally interact with the G-CSF receptor. Jak2 primarily enlists members of the signal transducer and activator of transcription (STAT) family and Lyn phosphorylates a number of adaptor molecules, which link the G-CSF receptor to phosphatidylinositol (PI) 3'-kinase and extracellular signal-regulated kinases (Erk) pathways. This review presents evidence that the Src kinases play a major role in the pathways of G-CSF-mediated proliferation, survival, and differentiation. Identification of Src-dependent pathways provides drug targets useful in the treatment of myeloid leukemias.
Sampson
Matthew
M
Department of Pediatrics, Children's Hospital of Philadelphia, USA.
Zhu
Quan-Sheng
QS
Corey
Seth J
SJ
D000818:Animals; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000201:enzymology; D010766:Phosphorylation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D014443:Tyrosine; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases