Biomaterial Database

GRB2 couples RhoU to epidermal growth factor receptor signaling and cell migration. 2011

Jin-San Zhang, and Alexander Koenig, and Charles Young, and Daniel D Billadeau

Division of Oncology Research and Schulze Center for Novel Therapeutics.

RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocalizes with EGF receptor (EGFR) on endosomes, which requires both its N- and C-terminal extension sequences. Moreover, RhoU physically associates with activated EGFR in a GRB2-dependent manner through specific proline-rich motifs within its N-terminus. Mutation of these proline-rich sequences or suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR, as well as EGF-stimulated RhoU GTP binding. In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2-EGFR complex. Taken together, the data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activation.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011992	Endosomes	Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.	Receptosomes,Endosome,Receptosome
D002465	Cell Movement	The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.	Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D048670	MAP Kinase Kinase 4	A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.	JN Kinase Kinase,JNK Kinase,JNK-Activating Protein Kinase,JNKK1 Protein Kinase,Jun Amino-Terminal Kinase Kinase,MEK4 Protein Kinase,Mitogen-Activated Protein Kinase Kinase 4,SAP Kinase Kinase 1,SAP Kinase-Extracellular Signal-Regulated Kinase Kinase 1,SAPK-ERK Kinase 1,SEK1 Protein Kinase,Stress-Activated Protein Kinase Kinase 1,JNK Activating Protein Kinase,Jun Amino Terminal Kinase Kinase,Kinase, JNKK1 Protein,Mitogen Activated Protein Kinase Kinase 4,Protein Kinase, JNK-Activating,Protein Kinase, JNKK1,Protein Kinase, MEK4,Protein Kinase, SEK1,SAP Kinase Extracellular Signal Regulated Kinase Kinase 1,SAPK ERK Kinase 1,Stress Activated Protein Kinase Kinase 1