FLT3 is a class III receptor tyrosine kinase that plays an important role in hematopoietic differentiation. Mutations in FLT3 that lead to constitutive activation are among the most common molecular lesions found in acute myeloid leukemia (AML) [, ]. FLT3 can be regulated by protein-tyrosine phosphatase DEP-1 []. An adaptor protein, Grb10, has been shown to bind both normal and oncogenic FLT3 and induces PI3K-Akt and STAT5 signalling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells [].
The flt3 (fms-related tyrosine kinase 3) ligand is a short chain cytokine with a 4 helical bundle fold. It is a type I membrane protein which stimulates the proliferation of of early hematopoeitic cells, and synergises well with other colony stimulating factors and interleukins.
This entry represents the SH2 domain found in SLAP/SLAP2.Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling []and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke []. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling []. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 []. SLAP2 acts as a negative regulator of FLT3 signaling [].
This entry represents the SH3 domain of SLAP. Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling []and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke []. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling []. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 []. SLAP2 acts as a negative regulator of FLT3 signaling [].
This entry represents Src-like-adapter 2 (SLAP2).Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling []and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke []. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling []. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 []. SLAP2 acts as a negative regulator of FLT3 signaling [].
This entry represents SLAP.Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling []and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke []. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling []. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 []. SLAP2 acts as a negative regulator of FLT3 signaling [].
Suppressor of cytokine signaling (SOCS) family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. However, SOCS6 does not interact with cytokine signaling intermediate molecules or inhibit cytokine receptor signaling. SOCS6 can interact with c-KIT, a receptor tyrosine kinase that mediates the cellular response to stem cell factor (SCF). SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells, suppressing c-KIT-dependent pathways []. SOCS6 negatively regulates receptor tyrosine kinase Flt3 activation, the downstream Erk signaling pathway, and cell proliferation [].
Suppressor of cytokine signaling (SOCS) family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. However, SOCS6 does not interact with cytokine signaling intermediate molecules or inhibit cytokine receptor signaling. SOCS6 can interact with c-KIT, a receptor tyrosine kinase that mediates the cellular response to stem cell factor (SCF). SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells, suppressing c-KIT-dependent pathways []. SOCS6 negatively regulates receptor tyrosine kinase Flt3 activation, the downstream Erk signaling pathway, and cell proliferation [].This entry represents the SH2 domain of SOCS6.
Tyrosine-protein kinase Fgr belongs to the SRC family of the Tyr protein kinases. It is a non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration [, , ]. It contains a protein kinase domain, an SH2 domain and an SH3 domain. Fgr interacts with tyrosine phosphorylated SYK, FLT3 and HCLS1 via its SH2 domain [].This entry represents the SH2 domain of Fgr.
This entry represents the SOCS box domain of SOCS6.Suppressor of cytokine signaling (SOCS) family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. However, SOCS6 does not interact with cytokine signaling intermediate molecules or inhibit cytokine receptor signaling. SOCS6 can interact with c-KIT, a receptor tyrosine kinase that mediates the cellular response to stem cell factor (SCF). SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells, suppressing c-KIT-dependent pathways []. SOCS6 negatively regulates receptor tyrosine kinase Flt3 activation, the downstream Erk signaling pathway, and cell proliferation [].The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions [, ].
