Src kinases in G-CSF receptor signaling

Abstract

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.