RAF proto-oncogene serine/threonine-protein kinase
ENTITY_REFERENCE_NOTES=Long Name: c-Raf-1 Synonym: MAPKKK Accession: P05928
ENTITY_REFERENCE_NOTES=Long Name: G protein-coupled receptor kinase 6 Synonym: Synonym not specified Accession: P05939
Guanine nucleotide-binding protein subunit gamma
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Guanine nucleotide-binding protein subunit beta-5
Inositol 1,4,5-trisphosphate receptor type 1
ENTITY_REFERENCE_NOTES=Long Name: phospholipase C Synonym: Synonym not specified Accession: P05933
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3
Dual specificity mitogen-activated protein kinase kinase 1
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
ENTITY_REFERENCE_NOTES= Long Name: G-protein, gamma subunit Synonym: Synonym not specified Accession: P05929
Dual-specificity mitogen-activated protein kinase kinase 2
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
Guanine nucleotide-binding protein G(q) subunit alpha
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
Raf-1 proto-oncogene, serine/threonine kinase
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase
ENTITY_REFERENCE_NOTES=Long Name: early growth response Synonym: KROX24,NGFIA Accession: P05931
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
ENTITY_REFERENCE_NOTES=Long Name: Angiotensin II Synonym: Synonym not specified Accession: P05935
ENTITY_REFERENCE_NOTES=Long Name: inositol 1,4,5-triphosphate receptor Synonym: Synonym not specified Accession: P05932
Inositol 1,4,5-trisphosphate receptor type 3
Guanine nucleotide-binding protein subunit beta-4
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
Inositol 1,4,5-trisphosphate receptor type 2
ENTITY_REFERENCE_NOTES=Long Name: mitogen-activated protein kinase Synonym: ERK Accession: P05937
ENTITY_REFERENCE_NOTES=Long Name: angiotensin type II 1a receptor Synonym: AGTR1,angiotensin receptor 1 Accession: P05924
ENTITY_REFERENCE_NOTES=Long Name: mitogen-activated or extracellular signal-regulated protein kinase Synonym: MAPKK,mitogen-activated protein kinase kinase Accession: P05926
ENTITY_REFERENCE_NOTES=Long Name: G protein-coupled receptor kinase 3 Synonym: ADRBK2,BARK2,beta-adrenergic receptor kinase 2 Accession: P05941
ENTITY_REFERENCE_NOTES=Long Name: RhoA GTPase Synonym: ARHA Accession: P05938
Dual specificity mitogen-activated protein kinase kinase 2
Guanine nucleotide-binding protein (G protein), beta 5
ENTITY_REFERENCE_NOTES=Long Name: beta-arrestin 1 Synonym: ARB1,ARRB1 Accession: P05925
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
Mitogen-activated protein kinase kinase 1
ENTITY_REFERENCE_NOTES=Long Name: G protein-coupled receptor kinase 5 Synonym: Synonym not specified Accession: P05940
ENTITY_REFERENCE_NOTES=Long Name: G-protein, alpha q subunit Synonym: Synonym not specified Accession: P05927
Inositol 1,4,5-trisphosphate receptor type 1 isoform 3
Guanine nucleotide-binding protein (G protein), q polypeptide
ENTITY_REFERENCE_NOTES=Long Name: ELK-1 member of EST oncogene family Synonym: Synonym not specified Accession: P05934
ENTITY_REFERENCE_NOTES=Long Name: beta-arrestin 2 Synonym: ARB2,ARRB2 Accession: P05923
Mitogen-activated protein kinase kinase 2
ENTITY_REFERENCE_NOTES=Long Name: protein kinase C Synonym: Synonym not specified Accession: P05942
ENTITY_REFERENCE_NOTES= Long Name: G-protein, beta subunit Synonym: Guanine nucleotide-binding protein, beta subunit Accession: P05930
MODEL_NOTES=Panther Pathway: P05911 The angiotensin 1a receptor mediates various angiotensin II (AngII)-dependent physiological responses such as vasoconstriction, smooth muscle cell motility and growth, and aldosterone secretion. By employing HEK-293 cells as a model system and utilizing b-arrestin and heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor kinase (GRK) RNAi technology, various novel aspects of angiotensin type II 1a receptor (AT1aR)-mediated extracellular signal-regulated protein kinase (ERK) activation have been uncovered. Stimulation of the receptor with its peptide ligand AngII results in the activation of Gaq/11 and the downstream kinase protein kinase C (PKC). This leads to the activation of the ERK cascade. The time course of this G protein-dependent ERK activation is rapid and transient, and the active ERK translocates to the nucleus to stimulate transcriptional pathways governed by Elk-1 activity and early growth response I (EGR-1) induction. The G protein-dependent ERK activation is not sensitive to b-arrestin RNAi and is eliminated by the addition of chemical inhibitors of PKC such as Ro-31-8425. The AngII-stimulated ERK pathway has an additional component that remains active for prolonged periods and is insensitive to PKC inhibitors. This pool of ERK is completely sensitive to b-arrestin 2 siRNA and remains excluded from the nucleus. b-arrestin 2-complexed ERK is targeted to endosomal compartments, where it presumably phosphorylates cytosolic substrates. Quite interestingly, b-arrestin 2-dependent ERK activation occurs only when b-arrestin 2 is recruited to GRK5- and/or GRK6- phosphorylated receptors. Depletion of cellular GRK5 or GRK6 isoforms results in complete inhibition of b-arrestin 2-dependent ERK activation, whereas depletion of the other GRK isoforms (GRK2 and 3) does not affect b-arrestin 2-dependent pERK, or rather even increases it. However, GRK2/3 are the primary kinases responsible for the bulk of receptor phosphorylation and overall b-arrestin recruitment to the receptor. Thus, the b-arrestin 2-dependent ERK pathway is associated with a specific b-arrestin 2 conformation induced by the GRK5/6-phosphorylated state of the receptor and not merely with b-arrestin recruitment to the receptor. Quite unexpectedly, b-arrestin 1 siRNA treatment enhances ERK activation elicited by b-arrestin 2-dependent mechanisms, suggesting that at physiological levels, b-arrestin 1 may act as a "dominant-negative" leading to inhibition of b-arrestin 2-dependent pERK. Whereas b-arrestin 2 can engage the ERK pathway independent of G proteins, b-arrestin 1 stimulates the small guanosine triphosphatase (GTPase) RhoA cooperatively with Gaq/11, leading to cytoskeletal changes and stress fiber formation. This pathway is adapted from the same pathway in STKE. Medline=12582207 Medline=12949261 Medline=14711824 Medline=15205453 Medline=15355986 Medline=15611106 Medline=15671181 Website=http://stke.sciencemag.org/cgi/cm/stkecm;CMP_16109 PMID: 12582207 PMID: 12949261 PMID: 14711824 PMID: 15205453 PMID: 15355986 PMID: 15611106 PMID: 15671181
ENTITY_REFERENCE_NOTES=Long Name: G protein-coupled receptor kinase 2 Synonym: ADRBK1,BARK1,beta-ARK1,beta-adrenergic receptor kinase 1 Accession: P05943