| Modification Notes |
The production, survival and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor M-CSF through its tyrosine kinase receptor Fms. Binding of M-CSF to Fms induces the tyrosine phosphorylation and association of SH2-containing inositol phosphatase SHIP with the phosphotyrosine-binding domain of Shc. The SHIP protein hydrolyzes PtdIns P3 to PtdIns Ps and results in strong inhibition of cell growth. SHIP is also a target for CD28, suggesting that SHIP may be involved in the regulation of T cell activation. SHIP has several splice variants and is expressed during hematopoiesis and spermatogenesis. SHIP-2, a homolog of SHIP, is expressed in both hemopoietic and non-hemopoietic cells. In addition to T and B cells, spleen, thymus and lung are shown to coexpress SHIP and SHIP-2. SHIP is also expressed in fibroblasts, heart, skeletal muscle and different brain areas and its expression is enhanced in TSH and EGF-stimulated cells. Like SHIP, SHIP-2 is tyrosine-phosphorylated and associates with Shc after ligation of the B-cell receptor to FcgRII. SHIP-2 causes cell cycle arrest in G1 phase in glioblastoma cells and plays a negative role in regulating the PI 3-kinase-PI 3-kinase B pathway. Both SHIP and SHIP-2 mediate FcgRIIB signaling, including inhibition of proliferation. |
