RAPID COMMUNICATION Tryptophan 650 of Human Granulocyte Colony-Stimulating Factor (G-CSF) Receptor, Implicated in the Activation of JAK2, Is Also Required for G-CSF-Mediated Activation of Signaling Complexes of the p2lras Route

Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p2lras route through interaction with its specific receptor (G-CSF-RI. The cytoplasmic membrane-proximal region of GCSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAW. In contrast, activation of Shc and Syp, signaling molecules implicated in the p2lras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSFinduced activation of signaling complexes of the p2lras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G-CSF-R mutant was con-