Translation - Translation regulation by Alpha-1 adrenergic receptors

Click on a target from the pathway image to view related information. Zoom     View Legend

photo_map
 


Human PrimePCR Selections
photo_fpc
Alpha-1 Adrenergic Receptor Regulation H96

Predesigned 96-well panel for use with SYBR® Green

 

List Price:  $394.00

 

Your Price : Log In

photo_fpc
Alpha-1 Adrenergic Receptor Regulation H384

Predesigned 384-well panel for use with SYBR® Green

 

List Price:  $523.00

 

Your Price : Log In

Translation regulation by Alpha-1 adrenergic receptors

Subtype alpha-1 adrenergic receptors consist of Alpha-1A adrenergic receptor, Alpha-1B adrenergic receptor and Alpha-1D adrenergic receptor. Noradrenaline-activated alpha-1 adrenergic receptors participate in many physiological processes, e.g., in translation activation [1], [2]

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

IP3 interacts with Inositol 1,4,5-triphosphate receptor type 3 (IP3 receptor) of the endoplasmic reticulum, and this leads to Ca('2+) release. Elevated Ca('2+) level activates Calmodulin / Calcium/calmodulin-dependent protein 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 2 domain 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 to Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). Presumably, then PtdIns(3,4,5)P3 then activates Shc / SOS / H-Ras. H-Ras then activates v-raf-1 murine leukemia viral oncogene homolog 1 (c-Raf-1) / Mitogen-activated protein kinase kinases 1 and 2 (MEK1(MAP2K1) and MEK2(MAP2K2))/ Mitogen activated protein kinase 1 (ERK2(MAPK1)) [1], [10].

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

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

Also, mTOR activates Eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) release from Eukaryotic translation initiation factor 4E (eIF4E) that in turn activates group Eukaryotic translation initiation factor 4 gamma (eIF4G1/3)/ Eukaryotic translation initiation factor 4A (eIF4A) [1], [10], [13]. PKC-delta seems participate in activation of mTOR and inhibition of 4E-BP1 [11]. PKC-delta phosphorylates 4E-BP1 synergistically with mTOR [14].

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

References:

  1. Wang L, Proud CG
    Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes. Circulation research 2002 Nov 1;91(9):821-9
  2. Zhang Y, Yan J, Chen K, Song Y, Lu Z, Chen M, Han C, Zhang Y
    Different roles of alpha1-adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats. Clinical and experimental pharmacology & physiology 2004 Sep;31(9):626-33
  3. Gurdal H, Seasholtz TM, Wang HY, Brown RD, Johnson MD, Friedman E
    Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta. Molecular pharmacology 1997 Dec;52(6):1064-70
  4. Hu ZW, Shi XY, Lin RZ, Hoffman BB
    Contrasting signaling pathways of alpha1A- and alpha1B-adrenergic receptor subtype activation of phosphatidylinositol 3-kinase and Ras in transfected NIH3T3 cells. Molecular endocrinology (Baltimore, Md.) 1999 Jan;13(1):3-14
  5. Ponicke K, Heinroth-Hoffmann I, Becker K, Osten B, Brodde OE
    Gq/11-coupled receptors and protein synthesis in rat cardiomyocytes: role of Gi-proteins and protein kinase C-isozymes. Naunyn-Schmiedeberg's archives of pharmacology 1999 Sep;360(3):301-8
  6. Arthur JF, Matkovich SJ, Mitchell CJ, Biden TJ, Woodcock EA
    Evidence for selective coupling of alpha 1-adrenergic receptors to phospholipase C-beta 1 in rat neonatal cardiomyocytes. The Journal of biological chemistry 2001 Oct 5;276(40):37341-6
  7. Della Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ
    Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase. The Journal of biological chemistry 1997 Aug 1;272(31):19125-32
  8. Gentili C, Morelli S, Russo De Boland A
    Involvement of PI3-kinase and its association with c-Src in PTH-stimulated rat enterocytes. Journal of cellular biochemistry 2002;86(4):773-83
  9. Kubo H, Hazeki K, Takasuga S, Hazeki O
    Specific role for p85/p110beta in GTP-binding-protein-mediated activation of Akt. The Biochemical journal 2005 Dec 15;392(Pt 3):607-14
  10. Wang L, Gout I, Proud CG
    Cross-talk between the ERK and p70 S6 kinase (S6K) signaling pathways. MEK-dependent activation of S6K2 in cardiomyocytes. The Journal of biological chemistry 2001 Aug 31;276(35):32670-7
  11. Wang L, Rolfe M, Proud CG
    Ca(2+)-independent protein kinase C activity is required for alpha1-adrenergic-receptor-mediated regulation of ribosomal protein S6 kinases in adult cardiomyocytes. The Biochemical journal 2003 Jul 15;373(Pt 2):603-11
  12. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP
    Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005 Apr 22;121(2):179-93
  13. Averous J, Proud CG
    When translation meets transformation: the mTOR story. Oncogene 2006 Oct 16;25(48):6423-35
  14. Kumar V, Pandey P, Sabatini D, Kumar M, Majumder PK, Bharti A, Carmichael G, Kufe D, Kharbanda S
    Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation. The EMBO journal 2000 Mar 1;19(5):1087-97
  15. Rybkin II, Cross ME, McReynolds EM, Lin RZ, Ballou LM
    alpha(1A) adrenergic receptor induces eukaryotic initiation factor 4E-binding protein 1 phosphorylation via a Ca(2+)-dependent pathway independent of phosphatidylinositol 3-kinase/Akt. The Journal of biological chemistry 2000 Feb 25;275(8):5460-5
  16. Ballou LM, Jiang YP, Du G, Frohman MA, Lin RZ
    Ca(2+)- and phospholipase D-dependent and -independent pathways activate mTOR signaling. FEBS letters 2003 Aug 28;550(1-3):51-6

Target Details

Click on a target from the pathway image to view related information.

[ Close ]
Click here to print
[ Close ]
Click here to print
 

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined