Src kinases in G-CSF receptor signaling

The Granulocyte Colony- Stimulating Factor ( GCSF) 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.