The major translational product of the v-Fms oncogene, originally isolated from the McDonough strain of feline sarcoma virus, has been identified as a glycoprotein with intrinsic tyrosine kinase activity. The v-Fms human cellular homolog, c-Fms, has been molecularly cloned and mapped to band q34 on chromosome 5, and identified as the receptor for hematopoietic ligand, CSF-1. Ligand-induced activation of the intrinsic CSF-1R protein tyrosine kinase triggers its interaction with cytoplasmic effector molecules. One such effector molecule, SHIP-1 p145 (SH2-containing-inositol phosphatase), associates with activated Fms. SHIP-1 contains two phosphotyrosine-binding domains (PTB), a unique amino terminal SH2 domain, a proline-rich region, and two highly conserved motifs found among inositol phosphate 5-phosphatases. SHIP-1 displays both phosphatidylinositol 3,4,5-triphosphate and inositol 1,3,4,5-tetrakisphosphate polyphosphate 5-phosphatase activity. Evidence suggests that SHIP-1 may modulate Ras signaling in addition to inositol signaling pathways.