Dopamine D1-Like Receptor Family Signaling Pathways

Click on each of the dopamine receptor families below to see the signaling pathways activated by receptors in that family. Click on DARPP-32 to view the phosphorylation sites on DARPP-32 with the respective kinases.

NR1/NR2B
NR1/NR2B
N-Type
Ca2+
Channel
N-Type
Ca2+
Channel
Dopamine
Dopamine
Dopamine D1-Like
Receptor Family
Dopamine D1-Like
Receptor Family
Dopamine
D5 R/DRD5
Dopamine
D5 R/DRD5
Dopamine
Dopamine
Dopamine
D1 R/DRD1
Dopamine
D1 R/DRD1
Dopamine
D2 R/DRD2
Dopamine
D2 R/DRD2
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RasGRF1
RasGRF1
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Ras-GDP
Ras-GDP
Ras-GTP
Ras-GTP
Raf
Raf
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CDK5
CDK5
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PP1
PP1
MEK1/2
MEK1/2
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PTPN5
PTPN5
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ERK1/2
ERK1/2
RSK
RSK
RSK
RSK
ERK1/2
ERK1/2
MSK1/2
MSK1/2
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CBP
CBP
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CREB
CREB
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CREB
CREB
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Elk-1
Elk-1
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SRF
SRF
Src
Family
Kinase
Src
Family
Kinase

Internalization

Internalization

G beta gamma
G beta gamma
G alphas/olf
G alphas/olf
PP2A
PP2A
Calcineurin
Calcineurin
Adenylyl
Cyclase
Adenylyl
Cyclase
PDE
PDE
cAMP
cAMP
PKA
PKA
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DARPP-32
DARPP-32
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T34
T34
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Calcineurin
Calcineurin
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DARPP-32
DARPP-32
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T34
T34
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PP1
PP1
PKA
PKA
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Histone H3
Histone H3
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CBP
CBP
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CREB
CREB
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Increase Activity
  • NMDA Receptors
  • AMPA Receptors
  • L-Type Ca2+
    Channels

Increase Activity
  • NMDA Receptors
  • AMPA Receptors
  • L-Type Ca2+
    Channels

Decrease Activity
  • Nav Channels
  • Kir Channels
  • N-, P/Q-Type Ca2+
    Channels

Decrease Activity
  • Nav Channels
  • Kir Channels
  • N-, P/Q-Type Ca2+
    Channels

Nuclear Translocation

Nuclear Translocation

G alphaq
G alphaq
PLC
PLC
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PIP2
PIP2
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DAG
DAG
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IP3
IP3
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IP3 Receptor
IP3 Receptor
PKC
PKC
GSK-3
GSK-3
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CDK5
CDK5
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DARPP-32
DARPP-32
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Ca2+/Calmodulin
Ca2+/Calmodulin
CaM Kinase II
CaM Kinase II
CaM Kinase II
CaM Kinase II

Dopamine (DA) is the dominate catecholamine neurotransmitter in the brain. It participates in a number of functions such as locomotion, memory, emotional and motivated behaviors, and neuroendocrine regulation. DA levels have been implicated in numerous neurological and psychiatric disorders including Parkinson’s disease, Huntington's disease, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, and Tourette's syndrome.

DA exerts its effects through five G protein-coupled receptors that are divided into two families based on structure and biological response: D1- and D2-like receptor families. The D1-like receptors, Dopamine D1 Receptor/DRD1 and Dopamine D5 Receptor/DRD5, share 80% amino acid (aa) sequence homology in their transmembrane domains, while the D2-like receptors, Dopamine D2 Receptor/DRD2, Dopamine D3 Receptor/DRD3, and Dopamine D4 Receptor/DRD4, are less homologous. The transmembrane regions of the D2 receptor share 75% and 53% aa sequence homology with the transmembrane domains of the D3 and D4 receptors, respectively. The D1 and D2 receptors are the most abundant dopamine receptor subtypes in the brain and exhibit broad expression patterns. The highest expression levels of the D1 receptor are observed in the caudate-putamen, nucleus accumbens, substantia nigra, olfactory bulb, amygdala, and frontal cortex. The highest levels of the D2 receptor are found in the caudate-putamen, nucleus accumbens, olfactory tubercle, substantia nigra, ventral tegmental area, hypothalamus, septum, amygdala, hippocampus, and cortical areas.

Dopamine D1-Like Receptor Family Signaling Pathways background image 1