Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
Inorganic ion
Predicted metabolite or user's structure
Generic receptor
Receptors with enzyme activity

Normal process
Pathological process
Covalent modifications
Transcription regulation
MicroRNA binding
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Translation Translation regulation by Alpha-1 adrenergic receptors

Log In to Post A Comment

Translation Translation regulation by Alpha-1 adrenergic receptors

Translation regulation by Alpha-1 adrenergic receptors

Subtype alpha-1 adrenergic receptors consists of Alpha-1A adrenergic receptor,Alpha-1B adrenergic receptor and Alpha-1D adrenergic receptor.Noradrenaline -activated alpha-1 adrenergic receptors participate in manyphysiological processes including translation activation [1], [2], [2]

These adrenergic receptors activate different Guanine nucleotide binding proteins(G-proteins). For example, all three receptors interact with G-protein alpha-q andG-protein alpha-11 [3], [4], [1]. Alpha-1Badrenergic receptor acts through G-protein beta/gamma of pertussistoxin-sensitive Alpha activating activity polypeptide O ( G-protein alpha-o )[3], [5]. Then, G-proteins activate Phospholipase C beta 1 (PLC-beta1 ) [6]. PLC-beta1 hydrolyzesPhosphatidylinositol-4,5-bisphosphate ( PtdIns(4,5)P2 ) to produce Inositol1,4,5-trisphosphate ( IP3 ) and 1,2-diacyl-glycerol ( DAG ).

IP3 interacts with Inositol 1,4,5-triphosphate receptor type 3 ( IP3receptor ) of the endoplasmic reticulum, and this leads to Ca('2+) release.Elevated Ca('2+) level activates Calmodulin/ Calcium/calmodulin-dependentprotein kinase II ( CaMK II )/ PTK2B protein tyrosine kinase 2 beta (Pyk2(FAK2) )/ v-src sarcoma viral oncogene homolog ( c-Src ) [7]. c-Src can activate Phosphoinositide-3-kinase, regulatory subunit 1(alpha) ( PI3K reg class IA (p85-alpha) )/ PI3K cat class IA (p110-beta)directly [4], [8], [9] or via SHC (Src homology 2domain containing) transforming protein 1 ( Shc )/ Son of sevenless homolog (SOS )/ v-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras ) [4].

Activated PI3K catalyzes transformation of PtdIns(4,5)P2 toPhosphatidylinositol-3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ). Presumably, thenPtdIns(3,4,5)P3 activates Shc/ SOS/ H-Ras. After that,H-Ras activates v-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1)/ Mitogen-activated protein kinase kinases 1 and 2 ( MEK1(MAP2K1) andMEK2(MAP2K2) )/ Mitogen activated protein kinase 1 ( ERK2(MAPK1) ) [10], [1].

In addition, Protein kinase C, delta and epsilon ( PKC-delta andPKC-epsilon ) are believed to be activated by DAG [5], [11] and can stimulate Pyk2(FAK2)/ PI3K/ ERK2(MAPK1) asdescribed [10], [8], [1] .

ERK2(MAPK1) activates Tuberous sclerosis 2 ( Tuberin ) [12]/ Ras homolog enriched in brain ( RHEB2 )/ FK506 binding protein 12-rapamycinassociated protein 1 ( mTOR )/ Ribosomal protein S6 kinase 70kDa polypeptide 1and 2 ( p70 S6 kinase1 and p70 S6 kinase2 )/ Eukaryotic elongationfactor-2 kinase ( eEF2K )/ Eukaryotic translation elongation factor 2 (eEF2 ).

Also, mTOR activates Eukaryotic translation initiation factor 4E bindingprotein 1 ( 4E-BP1 ) release from Eukaryotic translation initiation factor 4E (eIF4E ), that, in turn, activates group Eukaryotic translation initiation factor 4gamma ( eIF4G1/3 )/ Eukaryotic translation initiation factor 4A ( eIF4A )[10], [1], [13]. PKC-delta seems to have moreinfluence on the mTOR activation, and have excusive influence on 4E-BP1[11], in this case it phosphorylates 4E-BP1 synergistically withmTOR [14].

Moreover, Alpha-1A adrenergic receptor may participate in protein synthesisstimulation via Pyk2(FAK2) )/ c-Src/ Phospholipase D1 and D2 pathway (PLD1 and PLD2 ) [15], [16]. PLD1 andPLD2 participate in reaction of Phosphatidic acid production, which thenactivates mTOR, thus stimulating translation via eEF2 and/or eIF4A[16], [13].