KSR1 Antibody Phospho (pS404)

Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.

Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that interacts directly with MEK and MAPK. It has been shown that KSR1 translocates from the cytoplasm to the cell surface in response to growth factor treatment and that this process is regulated by MARK3 (1). MARK3 phosphorylates serine 309 and serine 404 on KSR1. While, PPP2CA dephosphorlyates serine 404 on KSR1. MARK3 seems to be a positive regulator of the beta-catenin pathway and an inhibitor of the JNK pathway. These findings show that MARK3, a regulator of polarity, is also a modulator of Wnt-beta-catenin signalling, indicating a link between two important developmental pathways (2).

A synthetic phospho-peptide corresponding to residues surrounding Serine 404 of human KSR1 was used as immunogen

Rabbit

50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

1. Muller J, et al. Mol Cell 8(5):983-93, 2001.<br>2. Sun TQ, et al. Nat Cell Biol 3(7):628-36, 2001.<br>

Human

Disabled homolog 2, DOC-2, Differentially-expressed protein 2, DAB2, DOC2

WB~~1:500~2000

Function Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containg non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor- mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin- mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr- 419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor. Cellular_Location Cytoplasm. Cytoplasmic vesicle, clathrin- coated vesicle membrane. Membrane, clathrin-coated pit Note=Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm Tissue_Location Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Expressed in kidney proximal tubular epithelial cells (at protein level)