Development - Dopamine D2 receptor transactivation of EGFR

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Dopamine D2 Receptor Transactivation of EGFR H96

Predesigned 96-well panel for use with SYBR® Green

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Dopamine D2 Receptor Transactivation of EGFR H384

Predesigned 384-well panel for use with SYBR® Green

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Dopamine D2 receptor transactivation of EGFR

Dopamine is a major transmitter and neuromodulator in the CNS. This transmitter mediates its signaling through GPCRs of which the Dopamine D2 receptor class of dopamine receptors is a common target for most antipsychotics. Dopamine can also transactivate members of receptor tyrosine kinases family, such EGFR.

Dopamine D2 receptor transactivation of EGFR implicates c-Src via at least two mechanisms: direct phosphorylation of EGFR and/or phosphorylation of some matrix metalloproteinases (e.g. ADAM12) [1], [2], [3].

EGFR leads to distinct downstream signaling events, one of which is mediated by transactivation of EGFR via ERK1 (MAPK3), ERK2 (MAPK1) pathways [1], [2], [4].

After EGFR phosphorylation, the receptor recruits adaptor proteins Shc and GRB2. In addition, Shc may be activated via Phosphoinositide-3-kinase. Activated Shc and GRB2 recruit SOS to the H-Ras. This results in rapid activation of H-Ras and subsequent activation of c-Raf-1/ MEK1(MAP2K1) and MEK2(MAP2K2), ERK2 (MAPK1) cascade [2], [3].

In addition, EGFR may activate PI3K cat class IA/ AKT(PKB) and thus, regulate cell negative regulation of neuron apoptosis [1].

Objects list:

ADAM12	Disintegrin and metalloproteinase domain-containing protein 12
AKT(PKB)	AKT(PKB) Protein group
Dopamine	Chemical IUPAC name 4-(2-Aminoethyl)benzene-1,2-diol
Dopamine D2 receptor	D(2) dopamine receptor
EGFR	Epidermal growth factor receptor
ERK1 (MAPK3)	Mitogen-activated protein kinase 3
ERK2 (MAPK1)	Mitogen-activated protein kinase 1
GRB2	Growth factor receptor-bound protein 2
H-Ras	GTPase HRas
MEK1(MAP2K1)	Dual specificity mitogen-activated protein kinase kinase 1
MEK2(MAP2K2)	Dual specificity mitogen-activated protein kinase kinase 2
PI3K cat class IA	The catalytic subunit of phosphatidylinositol 3-kinase subgroups IA Protein group
SOS	SOS Protein group
Shc	SHC-transforming protein 1
c-Raf-1	RAF proto-oncogene serine/threonine-protein kinase
c-Src	Proto-oncogene tyrosine-protein kinase Src

References:

Nair VD, Sealfon SC
Agonist-specific transactivation of phosphoinositide 3-kinase signaling pathway mediated by the dopamine D2 receptor. The Journal of biological chemistry 2003 Nov 21;278(47):47053-61
Wang C, Buck DC, Yang R, Macey TA, Neve KA
Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases. Journal of neurochemistry 2005 May;93(4):899-909
Ohtsu H, Dempsey PJ, Eguchi S
ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. American journal of physiology. Cell physiology 2006 Jul;291(1):C1-10
Beom S, Cheong D, Torres G, Caron MG, Kim KM
Comparative studies of molecular mechanisms of dopamine D2 and D3 receptors for the activation of extracellular signal-regulated kinase. The Journal of biological chemistry 2004 Jul 2;279(27):28304-14

Target Details

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Terms and Conditions

GeneCode	Dopamine D2 Receptor Transactivation of EGFR H96	Dopamine D2 Receptor Transactivation of EGFR H384
ADAM12	✓	✓
AKT1	✓	✓
AKT2	✓	✓
AKT3	✓	✓
DRD2	✓	✓
EGFR	✓	✓
GAPDH	✓	✓
GNAI1	✓	✓
GNB1	✓	✓
GNB3	✓	✓
GRB2	✓	✓
HBEGF	✓	✓
HPRT1	✓	✓
HRAS	✓	✓
MAP2K1	✓	✓
MAP2K2	✓	✓
MAPK1	✓	✓
MAPK3	✓	✓
PIK3CA	✓	✓
PIK3CB	✓	✓
PIK3CD	✓	✓
PIK3R1	✓	✓
RAF1	✓	✓
SHC1	✓	✓
SOS1	✓	✓
SRC	✓	✓
TBP	✓	✓

GeneCode	Dopamine D2 Receptor Transactivation of EGFR M96	Dopamine D2 Receptor Transactivation of EGFR M384
Adam12	✓	✓
Akt1	✓	✓
Akt2	✓	✓
Akt3	✓	✓
Drd2	✓	✓
Egfr	✓	✓
Gapdh	✓	✓
Gnai1	✓	✓
Gnb1	✓	✓
Gnb3	✓	✓
Grb2	✓	✓
Hbegf	✓	✓
Hprt	✓	✓
Hras1	✓	✓
Map2k1	✓	✓
Map2k2	✓	✓
Mapk1	✓	✓
Mapk3	✓	✓
Pik3ca	✓	✓
Pik3cb	✓	✓
Pik3cd	✓	✓
Pik3r1	✓	✓
Raf1	✓	✓
Shc1	✓	✓
Sos1	✓	✓
Src	✓	✓
Tbp	✓	✓

GeneCode	Dopamine D2 receptor transactivation of EGFR R96	Dopamine D2 receptor transactivation of EGFR R384
Adam12	✓	✓
Akt1	✓	✓
Akt2	✓	✓
Akt3	✓	✓
Drd2	✓	✓
Egfr	✓	✓
Gapdh	✓	✓
Gnai1	✓	✓
Gnb1	✓	✓
Gnb3	✓	✓
Grb2	✓	✓
Hbegf	✓	✓
Hprt1	✓	✓
HRAS1	✓	✓
Map2k1	✓	✓
Map2k2	✓	✓
Mapk1	✓	✓
Mapk3	✓	✓
Pik3ca	✓	✓
Pik3cb	✓	✓
Pik3cd	✓	✓
Pik3r1	✓	✓
Raf1	✓	✓
Shc1	✓	✓
Sos1	✓	✓
Src	✓	✓
Tbp	✓	✓

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