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Literature summary for 3.6.5.1 extracted from
- Signalling mechanisms of RhoGTPase regulation by the heterotrimeric G proteins G12 and G13 (2011), J. Biochem., 150, 357-369.
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Caenorhabditis elegans | calcium-independent PKCtheta/delta is a potential downstream target of Galpha12 | ? | - |
? |  |
| additional information | Homo sapiens | Galpha12 and Galpha13 couple with G-protein coupled receptors, GPCRs, for various ligands, e.g. angiotensin II, endothelin, thrombin, bombesin, thromboxane A2, sphingosine-1-phosphate, and lysophosphatidic acid. The coupling specificity between G12 and G13 is usually not strict and most of these ligands can activate both G12 and G13. The RH domain of PDZ-RhoGEF interacts with Galpha13 through multiple intermolecular interfaces. One point of contact is centred on an Ile-Ile-Gly motif found N-terminal to the RGS box. This motif forms multiple contacts with the alpha helical domain of Galpha13, and is conserved in other RH-RhoGEFs. Additionally, Galpha13 interacts with an acidic stretch of residues N-terminal to the core RGS box of PDZ-RhoGEF, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Caenorhabditis elegans | - |
- |
- |
| Drosophila melanogaster | - |
- |
- |
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| lipoprotein | both Galpha12 and 13 are subjected to palmitoylation at cysteine residues near their N-terminus, palmitoylation of Galpha13 is required for its association with the plasma membrane and its ability to activate RhoA through p115RhoGEF. Palmitoylated Galpha12 but not Galpha13 localizes in lipid rafts | Homo sapiens |
| additional information | Galpha12 and Galpha13 are not myristoylated because they lack a glycine residue as the second amino acid residue | Homo sapiens |
| phosphoprotein | phosphorylation of Galpha subunits is an important modification that regulates their function. Galpha12 is a substrate for phosphorylation by protein kinase C. Endogenous Ga12 in human platelets is phosphorylated within the first 50 N-terminal amino acid residues in response to PMA, thrombin and the TXA2 receptor agonist U46619. Phosphorylated Galpha12 loses its affinity for Gbetagamma, and the association with Gbetagamma reciprocally inhibits the phosphorylation of Ga12 by protein kinase C. Endogenous Galpha13 in platelets is phosphorylated in response to PMA, although not in vitro. PKC-mediated phosphorylation of Ga13 in cell might require additional factors | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| blood platelet | - |
Homo sapiens | - |
| additional information | both Galpha12 and Galpha13 are expressed ubiquitously | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | calcium-independent PKCtheta/delta is a potential downstream target of Galpha12 | Caenorhabditis elegans | ? | - |
? | |
| additional information | Galpha12 and Galpha13 couple with G-protein coupled receptors, GPCRs, for various ligands, e.g. angiotensin II, endothelin, thrombin, bombesin, thromboxane A2, sphingosine-1-phosphate, and lysophosphatidic acid. The coupling specificity between G12 and G13 is usually not strict and most of these ligands can activate both G12 and G13. The RH domain of PDZ-RhoGEF interacts with Galpha13 through multiple intermolecular interfaces. One point of contact is centred on an Ile-Ile-Gly motif found N-terminal to the RGS box. This motif forms multiple contacts with the alpha helical domain of Galpha13, and is conserved in other RH-RhoGEFs. Additionally, Galpha13 interacts with an acidic stretch of residues N-terminal to the core RGS box of PDZ-RhoGEF, overview | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterotrimer | - |
Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| G12 | - |
Drosophila melanogaster |
| G12 | - |
Homo sapiens |
| G12 | - |
Caenorhabditis elegans |
| G13 | - |
Drosophila melanogaster |
| G13 | - |
Homo sapiens |
| G13 | - |
Caenorhabditis elegans |
| heterotrimeric G protein | - |
Drosophila melanogaster |
| heterotrimeric G protein | - |
Homo sapiens |
| heterotrimeric G protein | - |
Caenorhabditis elegans |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | Galpha subunits are classified into four subfamilies, Gs, Gi, Gq and G12. Galpha12/13 and Galphaq are directly involved in the activation of RhoGTPases, molecular mechanisms for regulation of RhoGTPase activity through GPCR heterotrimeric G12/13-signalling pathways, overview. The G12/13-RH-RhoGEF signalling mechanism is well conserved over species | Drosophila melanogaster |
| evolution | Galpha subunits are classified into four subfamilies, Gs, Gi, Gq and G12. Galpha12/13 and Galphaq are directly involved in the activation of RhoGTPases, molecular mechanisms for regulation of RhoGTPase activity through GPCR heterotrimeric G12/13-signalling pathways, overview. The G12/13-RH-RhoGEF signalling mechanism is well conserved over species | Homo sapiens |
| evolution | Galpha subunits are classified into four subfamilies, Gs, Gi, Gq and G12. Galpha12/13 and Galphaq are directly involved in the activation of RhoGTPases, molecular mechanisms for regulation of RhoGTPase activity through GPCR heterotrimeric G12/13-signalling pathways, overview. The G12/13-RH-RhoGEF signalling mechanism is well conserved over species | Caenorhabditis elegans |
| malfunction | deletion of any component of the Galpha13-RhoGEF-RhoA-signalling pathway results in a similar phenotype consisting of embryonic lethality at the stage of gastrulation | Drosophila melanogaster |
| malfunction | overexpression of constitutively active Galpha12 or 13 induces several cellular effects which suggest stimulation of Rho activity in cells, such as formation of actin stress fibres or neurite retraction in neuronal cells. NIH3T3 transforming activity of constitutively active mutant of Galpha12 can be prevented by blocking its palmitoylation | Homo sapiens |
| additional information | Gbetagamma interacts with the N-terminal alpha helix of Galpha through one of the seven bladed propellers of the Gbeta subunit | Homo sapiens |
| physiological function | the G12/13-RH-RhoGEF signalling mechanism is involved in critical steps for cell physiology and disease conditions, including embryonic development, oncogenesis and cancer metastasis. alpha Subunits of G12 or G13 interact with members of the RH domain containing guanine nucleotide exchange factors for Rho (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling and RhoGTPase signalling, G12/13-mediated signalling is one mechanism to regulate RhoGTPase activity in response to extracellular stimuli. Wild-type Galpha12 is the only Galpha subunit that acts as an oncogene in NIH3T3 cells | Homo sapiens |
| physiological function | the G12/13-RH-RhoGEF signalling mechanism is involved in critical steps for cell physiology and disease conditions. alpha Subunits of G12 or G13 interact with members of the RH domain containing guanine nucleotide exchange factors for Rho (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling and RhoGTPase signalling, G12/13-mediated signalling is one mechanism to regulate RhoGTPase activity in response to extracellular stimuli | Drosophila melanogaster |
| physiological function | the G12/13-RH-RhoGEF signalling mechanism is involved in critical steps for cell physiology and disease conditions. alpha Subunits of G12 or G13 interact with members of the RH domain containing guanine nucleotide exchange factors for Rho (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling and RhoGTPase signalling, G12/13-mediated signalling is one mechanism to regulate RhoGTPase activity in response to extracellular stimuli | Caenorhabditis elegans |
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