Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rho, a member of the Ras superfamily of GTP-binding proteins, regulates actin polymerization resulting in the formation of stress fibers and the assembly of focal adhesions. In Swiss 3T3 cells, heterotrimeric G protein-coupled receptors for lysophosphatidic acid and gastrin releasing peptide stimulate Rho-dependent stress fiber and focal adhesion formation. The specific heterotrimeric G protein subunits mediating Rho-dependent stress fiber and focal adhesion formation have not been defined previously. We have expressed GTPase-deficient, constitutively activated G protein alpha subunits and mixtures of beta and gamma subunits in Swiss 3T3 cells. Measurement of actin polymerization and focal adhesion formation indicated that GTPase-deficient alpha 12 and alpha 13, but not the activated forms of alpha 12 or alpha q stimulated stress fiber and focal adhesion assembly. Combinations of beta and gamma subunits were unable to stimulate stress fiber or focal adhesion formation. G alpha 12- and alpha 13-mediated stress fiber and focal adhesion assembly was inhibited by botulinum C3 exoenzyme, which ADP-ribosylates and inactivates Rho, indicating that alpha 12 and alpha 13, but not other G protein alpha subunits or beta gamma complexes, regulate Rho-dependent responses. The results define the integration of G12 and G13 with the regulation of the actin cytoskeleton.
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PMID:G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly. 755 69

The expression of members of the Reg family of secreted lectin-like proteins is increased in response to stress, inflammation and damage in many tissues. In the stomach, Reg is located in enterochromaffin-like cells, where its expression is stimulated by the gastric hormone gastrin. We have examined the mechanisms by which gastrin stimulates expression of Reg-1. Deletional mutations of 2.1 to 0.1 kb of the rat Reg-1 promoter in a luciferase reporter vector were transiently transfected into gastric cancer AGS-G(R) cells. All promoter fragments tested showed similar relative increases in luciferase expression in response to gastrin (1 nM). The response to gastrin of the smallest (104 bp) construct was 4.2+/-0.4-fold over basal. These responses were reduced by Ro-32-0432, a protein kinase C inhibitor, by C3-transferase, a Clostridium botulinum toxin and a selective inhibitor of the Rho family GTPase RhoA, and by co-transfection with a dominant negative form of RhoA. Co-transfection with a constitutively active form of RhoA stimulated expression 11.6+/-1.7-fold over basal. Mutations through the 104 bp construct identified a C-rich element (C-79CCCTCCC-72) required for responses to gastrin, PKC (protein kinase C) and L63RhoA (the constitutively active form of human RhoA protein containing a glutamine-to-leucine substitution at position 63). EMSAs (electrophoretic-mobility-shift assays) using nuclear extracts of control and gastrin-stimulated AGS-G(R) cells and a probe spanning -86 to -64 bp revealed multiple binding proteins. There was no effect of gastrin on the pattern of binding. Supershift assays indicated that transcription factors Sp1 and Sp3 bound the C-rich sequence. We conclude that gastrin stimulates Reg expression via activation of PKC and RhoA, that a C-rich region (-79 to -72) is critical for the response and that Sp-family transcription factors bind to this region of the promoter.
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PMID:Control of expression of the lectin-like protein Reg-1 by gastrin: role of the Rho family GTPase RhoA and a C-rich promoter element. 1510 6