Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting
Background: GAS6 (Growth Arrest Specific gene 6) is a vitamin K-dependent ligand of the TAM (Tyro3, Axl and MerTK) RTK family. It has an N-terminal Gla domain containing multiple Asp gamma-carboxylation sites, followed by four EGF repeats and two C-terminal LG domains. Vitamin K mediates multiple gamma-carboxylations of glutamic acid residues in the GAS6 Gla domain. These modifications are required for GAS6 to to activate its receptor (1,2). The two C-terminal LG (SHBG) domains form a V-shaped structure and provide a direct binding site for receptor interaction. Among the TAM family members, GAS6 has high affinity for Axl and low affinity for Tyro3 and MerTK. Ligand/receptor interaction activates multiple downstream signaling pathways such as PI3K/AKT, STAT/SOCS, PLC/FAK, and Grb2/RAS, and promotes cell survival, proliferation, migration and differentiation (3,4). GAS6 has been implicated in cancer development and immune-related disorders (inflammation and multiple sclerosis), and as such has been identified as a potential therapeutic target (3-6).
Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting
Background: Slug (SNAI2) is a widely expressed transcriptional repressor and member of the Snail family of zinc finger transcription factors (1). Similar to the related Snail protein, Slug binds to the E-cadherin promoter region to repress transcription during development (2). The binding of Slug to integrin promoter sequences represses integrin expression and results in reduced cell adhesion (3). Down regulation of E-cadherin expression occurs during the epithelial-mesenchymal transition during embryonic development, a process also exploited by invasive cancer cells (4,5). The tumor suppressor protein p53 induces Slug expression in γ-irradiated cells; Slug protects damaged cells from apoptosis by repressing p53-induced transcription of the proapoptotic Bcl-2 family protein Puma (6). Deletion mutations in the corresponding Slug gene are associated with the pigmentation disorders Waardenburg Syndrome and Piebaldism, while a genetic duplication resulting in Slug overexpression is associated with a collection of congenital heart defects termed tetralogy of Fallot (7).
Application Methods: IHC-Leica® Bond™, Immunofluorescence (Frozen), Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation
Background: The protein phosphatase (PTP) receptor CD45 is a type I transmembrane protein comprised of a pair of intracellular tyrosine phosphatase domains and a variable extracellular domain generated by alternative splicing (1). The catalytic activity of CD45 is a function of the first phosphatase domain (D1) while the second phosphatase domain (D2) may interact with and stabilize the first domain, or recruit/bind substrates (2,3). CD45 interacts directly with antigen receptor complex proteins or activates Src family kinases involved in the regulation of T- and B-cell antigen receptor signaling (1). Specifically, CD45 dephosphorylates Src-family kinases Lck and Fyn at their conserved negative regulatory carboxy-terminal tyrosine residues and upregulates kinase activity. Conversely, studies indicate that CD45 can also inhibit Lck and Fyn by dephosphorylating their positive regulatory autophosphorylation site. CD45 appears to be both a positive and a negative regulator that conducts signals depending on specific stimuli and cell type (1). Human leukocytes including lymphocytes, eosinophils, monocytes, basophils, and neutrophils express CD45, while erythrocytes and platelets are negative for CD45 expression (4).
|Human, Monkey, Mouse, Rat|
Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting
Background: Nonmuscle myosin is an actin-based motor protein essential to cell motility, cell division, migration, adhesion, and polarity. The holoenzyme consists of two identical heavy chains and two sets of light chains. The light chains (MLCs) regulate myosin II activity and stability. The heavy chains (NMHCs) are encoded by three genes, MYH9, MYH10, and MYH14, which generate three different nonmuscle myosin II isoforms, IIa, IIb, and IIc, respectively (reviewed in 1). While all three isoforms perform the same enzymatic tasks, binding to and contracting actin filaments coupled to ATP hydrolysis, their cellular functions do not appear to be redundant and they have different subcellular distributions (2-5). The carboxy-terminal tail domain of myosin II is important in isoform-specific subcellular localization (6). Research studies have shown that phosphorylation of myosin IIa at Ser1943 contributes to the regulation of breast cancer cell migration (7).