Home LiteratureArticle Details
PMID: 7835339 Published · ppublish English Journal Article

A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities.

The EMBO journal ·Vol. 14 ·No. 2 ·1995-01-16 ·Pages 286-91

Homma Y, Emori Y

Abstract

We have cloned a novel regulator protein, p122, in the PLC-delta signalling pathway by screening a rat brain expression library with antiserum raised against purified phospholipase C-delta 1 (PLC-delta 1). This novel p122-RhoGAP binds to PLC-delta 1 and activates the phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolyzing activity of PLC-delta 1. As suggested by the deduced amino acid sequence, this regulator protein shows a similarity to the GTPase activating protein (GAP) homology region of Bcr and possesses GAP activity for RhoA, but not for Rac1; no guanine nucleotide exchange activity for RhoA and Rac1 was detected. These findings suggest that this novel RhoGAP is involved in the Rho signalling pathway, probably downstream of Rho activation, and mediates the stimulation of PLC-delta, which leads to actin-related cytoskeletal changes through the hydrolysis of PIP2, which binds to actin binding proteins such as gelsolin and profilin.

MeSH Terms
Amino Acid Sequence Animals Cloning, Molecular DNA, Complementary Enzyme Activation GTP-Binding Proteins/genetics,metabolism GTPase-Activating Proteins Hydrolysis Isoenzymes/metabolism Molecular Sequence Data Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates/metabolism Rats Sequence Homology, Amino Acid Signal Transduction Type C Phospholipases/metabolism
Chemicals
DNA, Complementary GTPase-Activating Proteins Isoenzymes Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates rho GTPase-activating protein Type C Phospholipases GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Homma Y
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Emori Y
References (43)
43 references, click to expand
  1. Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin.
    Nature. 1985 Apr 4-10;314(6010):472-4 PMID: 2984579
  2. Characterization of a promiscuous GTPase-activating protein that has a Bcr-related domain from Caenorhabditis elegans.
    J Biol Chem. 1994 Jan 14;269(2):820-3 PMID: 8288633
  3. Isolation and characterization of two different forms of inositol phospholipid-specific phospholipase C from rat brain.
    J Biol Chem. 1988 May 15;263(14):6592-8 PMID: 3360794
  4. bcr genes and transcripts.
    Oncogene. 1988 Feb;2(2):113-7 PMID: 3285291
  5. A novel phorbol ester receptor/protein kinase, nPKC, distantly related to the protein kinase C family.
    Cell. 1988 Jun 3;53(5):731-41 PMID: 3370672
  6. Computer programs for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands.
    Methods Enzymol. 1988;157:378-417 PMID: 3231093
  7. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells.
    EMBO J. 1989 Apr;8(4):1087-92 PMID: 2501082
  8. Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene.
    J Mol Biol. 1990 Jan 5;211(1):11-6 PMID: 2299665
  9. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases.
    Nature. 1990 Jan 25;343(6256):377-81 PMID: 1689011
  10. The actin-binding protein profilin binds to PIP2 and inhibits its hydrolysis by phospholipase C.
    Science. 1990 Mar 30;247(4950):1575-8 PMID: 2157283
  11. Inhibition of the interactions of cofilin, destrin, and deoxyribonuclease I with actin by phosphoinositides.
    J Biol Chem. 1990 May 25;265(15):8382-6 PMID: 2160454
  12. Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein.
    J Biol Chem. 1990 Jun 5;265(16):9373-80 PMID: 2111820
  13. Isolation and characterization of a gamma-type phosphoinositide-specific phospholipase C (PLC-gamma 2).
    Biochem J. 1990 Jul 1;269(1):13-8 PMID: 2165390
  14. The cellular functions of small GTP-binding proteins.
    Science. 1990 Aug 10;249(4969):635-40 PMID: 2116664
  15. Microinjection of recombinant p21rho induces rapid changes in cell morphology.
    J Cell Biol. 1990 Sep;111(3):1001-7 PMID: 2118140
  16. The GTPase superfamily: a conserved switch for diverse cell functions.
    Nature. 1990 Nov 8;348(6297):125-32 PMID: 2122258
  17. gCap39, a calcium ion- and polyphosphoinositide-regulated actin capping protein.
    Science. 1990 Dec 7;250(4986):1413-5 PMID: 2255912
  18. Regulation of phospholipase C-gamma 1 by profilin and tyrosine phosphorylation.
    Science. 1991 Mar 8;251(4998):1231-3 PMID: 1848725
  19. Purification of GTPase-activating protein specific for the rho gene products.
    J Biol Chem. 1991 Apr 25;266(12):7646-50 PMID: 1902224
  20. Post-translational modifications of the C-terminal region of the rho protein are important for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins.
    Oncogene. 1991 Apr;6(4):515-22 PMID: 1903193
  21. Bcr encodes a GTPase-activating protein for p21rac.
    Nature. 1991 May 30;351(6325):400-2 PMID: 1903516
  22. Purification and N-terminal sequence of the p21rho GTPase-activating protein, rho GAP.
    Biochem J. 1991 Jun 15;276 ( Pt 3):833-6 PMID: 1905930
  23. Identification of the human platelet GTPase activating protein for the CDC42Hs protein.
    J Biol Chem. 1991 Nov 5;266(31):20840-8 PMID: 1939135
  24. Effects of gelsolin on human platelet cytosolic phosphoinositide-phospholipase C isozymes.
    J Biol Chem. 1992 Apr 5;267(10):6488-94 PMID: 1313007
  25. Signal transduction through small GTPases--a tale of two GAPs.
    Cell. 1992 May 1;69(3):389-91 PMID: 1316238
  26. Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus.
    Cell. 1992 May 1;69(3):539-49 PMID: 1581965
  27. Phosphoinositide-binding peptides derived from the sequences of gelsolin and villin.
    J Biol Chem. 1992 Jun 15;267(17):11818-23 PMID: 1318302
  28. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.
    Cell. 1992 Aug 7;70(3):389-99 PMID: 1643657
  29. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  30. Diversity and versatility of GTPase activating proteins for the p21rho subfamily of ras G proteins detected by a novel overlay assay.
    J Biol Chem. 1992 Aug 15;267(23):16025-8 PMID: 1644791
  31. Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function.
    Nature. 1992 Sep 10;359(6391):150-2 PMID: 1326084
  32. A rho gene product in human blood platelets. II. Effects of the ADP-ribosylation by botulinum C3 ADP-ribosyltransferase on platelet aggregation.
    J Biol Chem. 1992 Oct 15;267(29):20921-6 PMID: 1400407
  33. Inhibitory effect of src homology (SH) 2/SH3 fragments of phospholipase C-gamma on the catalytic activity of phospholipase C isoforms. Identification of a novel phospholipase C inhibitor region.
    J Biol Chem. 1992 Oct 25;267(30):21844-9 PMID: 1328245
  34. A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins.
    Mol Cell Biol. 1992 Nov;12(11):5111-22 PMID: 1406685
  35. Multiple forms of phospholipase C isozymes and their activation mechanisms.
    Adv Second Messenger Phosphoprotein Res. 1992;26:35-61 PMID: 1419362
  36. A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs.
    Science. 1992 Oct 30;258(5083):812-5 PMID: 1439791
  37. Regulation of morphology by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in Swiss 3T3 cells.
    J Biol Chem. 1993 Jan 5;268(1):510-5 PMID: 8416955
  38. Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility.
    Mol Cell Biol. 1993 Jan;13(1):72-9 PMID: 8417362
  39. Inositol trisphosphate and calcium signalling.
    Nature. 1993 Jan 28;361(6410):315-25 PMID: 8381210
  40. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI).
    J Cell Biol. 1993 Mar;120(5):1187-95 PMID: 8436590
  41. Germ cell beta-chimaerin, a new GTPase-activating protein for p21rac, is specifically expressed during the acrosomal assembly stage in rat testis.
    J Biol Chem. 1993 Feb 25;268(6):3813-6 PMID: 8440677
  42. Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the ras-related protein p21rac derived by alternate splicing of the human n-chimerin gene, is selectively expressed in brain regions and testes.
    Mol Cell Biol. 1993 Aug;13(8):4986-98 PMID: 8336731
  43. Functional modification of a 21-kilodalton G protein when ADP-ribosylated by exoenzyme C3 of Clostridium botulinum.
    Mol Cell Biol. 1988 Jan;8(1):418-26 PMID: 3122025
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-01-16
Pages
286-91
Language
English
Region
England
NLM ID
8208664
PMCID
PMC398082
Subset
IM
Databases
GENBANK
D31962
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2