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This page, as it appeared on June 14, 2016, was featured in this article in the journal Biochemistry and Molecular Biology Education.

SHOC2-PP1C-MRAS

spinqualitylabelsall models SHOC2-MRAS-PP1C Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Introduction SHOC2-PP1C-MRAS (SMP) is a ternary holophosphotase complex formed by the individual proteins: SHOC2, PP1C, and MRAS. The SMP complex is involved in signaling the initiation of MAPK pathways, which is responsible for cellular growth and development, cell proliferation, and apoptosis (cite 1). Formation of this complex begins with an extracellular signal binding to a membrane embedded receptor tyrosine kinase receptor(RTK) . This causes membrane-bound MRAS to exchange GDP for GTP. Initiating the SMP complex formation at the plasma membrane consists of the SHOC2 and PP1C binding first. When the MRAS exchanges GDP to GTP, it then assembles with the combined SHOC2 and PP1C. Based on MRAS targeting, PP1C catalyzes the dephosphorylation of the N-terminal phosphoserine (NTpS) on the RAF complex leading to the amplification of MAPK signaling . In a normal cell, this would regulate cell proliferation but dysfunction in the ternary complex has shown signs to lead to tumor formation due to unregulated cell growth . Figure 1: Mechanism for Shoc2-MRAS-PP1C Figure 2: PP1C phosphorylates Serine 259. Overall Structure SHOC2 SHOC2 PP1C PP1C MRAS MRAS GTP-MRAS(full-image) GTP-MRAS(zoomed-in) Switch I-II (full-image) Switch I-II (zoomed-in) Key Ligand Interactions Figure 3: Electrostatic illustration of the amphipathic binding pocket of the LPA1 receptor. This binding pocket was revealed by cutting away the exterior or the protein. This binding pocket, located in the interior of the protein, has both polar and nonpolar regions. The blue and red coloration highlight the positively and negatively charged regions, respectively, and the white color shows the nonpolar region of the binding pocket. SHOC2 and PP1C Shoc2-PP1C SHOC2-PP1C Binding Pocket SHOC2 and MRAS SHOC2-MRAS(full-image) SHOC2-MRAS (residues) SHOC2-MRAS (surface) PP1C and MRAS PP1C (blue) and MRAS (white) PP1C and MRAS residue interactions Signaling Pathway PP1C Hydrophobic Patch and Active Site 3D structures of lysophosphatidic acid receptor 4z34, 4z35, 4z36 - hLPA1 + antagonist - human 2lq4 – hLPA1 second extracellular loop – NMR 4p0c – hLPA2/NHERF2 5xsz – LPA6A (mutant) – zebra fish Proteopedia Resources Category:Lysophosphatidic acid binding Category:Lysophosphatidic acid Butler University Proteopedia Pages See also: Receptor Transmembrane (cell surface) receptors G protein-coupled receptors

Student Contributors

Madeline Gilbert Inaya Patel Rushda Hussein