ArticleThe EMBO journal1999
PI 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 143 citations in OpenAlex.
- Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis.Toxins · 2026Review
- Intracellular Sphingosine-1-Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Review
- Noncanonical regulation of insulin-mediated ERK activation by phosphoinositide 3-kinase γ.Molecular biology of the cell · 2017Article
- Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors.PloS one · 2015Article
- Mechanisms linking obesity and cancer.Biochimica et biophysica acta · 2013Review
- Lysophosphatidic acid-induced p21Waf1 expression mediates the cytostatic response of breast and ovarian cancer cells to TGFβ.Molecular cancer research : MCR · 2011Article
- Differential regulation of protrusion and polarity by PI3K during neutrophil motility in live zebrafish.Developmental cell · 2010Article
- Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase Cbeta2 in the regulation of physiologic developmental hypertrophy and heart function.American journal of physiology. Heart and circulatory physiology · 2009Article
- Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor.Molecular biology of the cell · 2007Article
- RhoA-GTPase facilitates entry of Kaposi's sarcoma-associated herpesvirus into adherent target cells in a Src-dependent manner.Journal of virology · 2006Article
- Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks.Purinergic signalling · 2006Article
- Phosphorylation of adaptor protein-2 mu2 is essential for Na+,K+-ATPase endocytosis in response to either G protein-coupled receptor or reactive oxygen species.American journal of respiratory cell and molecular biology · 2006Article
- Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration.The Journal of cell biology · 2005Article
- Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia.Journal of human genetics · 2005Article
- Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells.Molecular and cellular biology · 2004Article
- Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 envelope glycoprotein gB induces the integrin-dependent focal adhesion kinase-Src-phosphatidylinositol 3-kinase-rho GTPase signal pathways and cytoskeletal rearrangements.Journal of virology · 2004Article
- Characterization of ERK1/2 signalling pathways induced by adenosine receptor subtypes in newborn rat cardiomyocytes.British journal of pharmacology · 2004Article
- Kaposi's sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase-PKC-zeta-MEK-ERK signaling pathway in target cells early during infection: implications for infectivity.Journal of virology · 2003Article
- Leucocyte chemotaxis: Examination of mitogen-activated protein kinase and phosphoinositide 3-kinase activation by Monocyte Chemoattractant Proteins-1, -2, -3 and -4.Clinical and experimental immunology · 2002Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptors coupled to the inhibitory G protein Gi, such as that for lysophosphatidic acid (LPA), have been shown to activate MAP kinase through a RAS-dependent pathway. However, LPA (but not insulin) has now been shown to activate MAP kinase in a RAS-independent manner in CHO cells that overexpress a dominant-negative mutant of the guanine nucleotide exchange protein SOS (CHO-DeltaSOS cells). LPA also induced the activation of MAP kinase kinase (MEK), but not that of RAF1, in CHO-DeltaSOS cells. The RAS-independent activation of MAP kinase by LPA was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by overexpression of a dominant-negative mutant of the gamma isoform of PI3K. Furthermore, LPA induced the activation of the atypical zeta isoform of protein kinase C (PKC-zeta) in CHO-DeltaSOS cells in a manner that was sensitive to wortmannin or to the dominant-negative mutant of PI3Kgamma, and overexpression of a dominant-negative mutant of PKC-zeta inhibited LPA-induced activation of MAP kinase. These observations indicate that Gi protein-coupled receptors induce activation of MEK and MAP kinase through a RAS-independent pathway that involves PI3Kgamma-dependent activation of atypical PKC-zeta.
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