Phospho-SHIP1 (Tyr1020)[Tyr1022] Antibody - #AF2403

Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression.

Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.

Cytoplasm. Cell membrane>Peripheral membrane protein. Membrane raft. Cytoplasm>Cytoskeleton. Membrane>Peripheral membrane protein.
Note: Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Translocates from the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner. Colocalizes with FC-gamma-RIIB receptor (FCGR2B) or FCGR3/CD16 at membrane ruffles. Tyrosine phosphorylation may also participate in membrane localization.

Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level).

Interacts with tyrosine phosphorylated form of SHC1. Interacts with tyrosine phosphorylated form of DOK1. Interacts with tyrosine phosphorylated form of DOK3 (By similarity). Interacts with tyrosine phosphorylated form of SLAMF1/CD150. Interacts with PTPN11 in response to IL-3 (By similarity). Interacts with receptor EPOR (By similarity). Interacts with receptors MS4A2/FCER1B and FCER1G (By similarity). Interacts with receptors FCGR2B and FCGR3 (By similarity). Interacts with receptor FCGR2A, leading to regulate gene expression during the phagocytic process (By similarity). Interacts with GRB2. Interacts with PLCG1 (By similarity). Interacts with tyrosine kinases SRC and TEC (By similarity). Interacts with c-Met/MET (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (By similarity). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity). Interacts with FCRL3 and FCRL6 (tyrosine phosphorylated form).

The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation (By similarity).

The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.

Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.