Cell. 2002 Nov 15;111(4):529-41.
Phospholipase C-gamma is required for agonist-induced Ca2+ entry.
Patterson, R. L., van Rossum, D. B., Ford, D. L., Hurt, K. J., Bae, S. S., Suh, P. G., Kurosaki, T., Snyder, S. H., Gill, D. L.,
["Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."]
["Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."]
We report here that PLC-gamma isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-gamma1 or a lipase-inactive mutant PLC-gamma1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-gamma1 was ineffective. RNA interference to deplete either PLC-gamma1 or PLC-gamma2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-gamma2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-gamma2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-gamma2 or a lipase-inactive PLC-gamma2 mutant. The results indicate a lipase-independent role of PLC-gamma in the physiological agonist-induced activation of Ca2+ entry.
PMID: 12437926
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
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| Experimental screening | Non-experimental screening | Reference | ||||||||
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| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPC3 |
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PLCƣ1 | Inference | Prediction | 12437926 | |||||
| TRPC4 |
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PLCƣ1 | Inference | Prediction | 12437926 | |||||
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Validation: In vitro validation
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| Assay with recombinant proteins | Reference | |||||||||
| TRP channel construct | Interactor construct | |||||||||
| TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
| TRPC3 |
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PLCƣ1 | Yeast two-hybrid | Human | 1-340 | Yeast | Rat | 750-1290 | Yeast | 12437926 |
| TRPC4 |
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PLCƣ1 | Yeast two-hybrid | Human | 1-330 | Yeast | Rat | 750-1290 | Yeast | 12437926 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPC3 |
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PLCƣ1 | Co-immunoprecipitation | HEK293T | Human | Full-length | Rat | Full-length | 12437926 | |
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Characterization
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| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPC3 |
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PLCƣ1 | Yeast two-hybrid | Human | 1-340 | Rat | 780-920 | 12437926 | ||
| TRPC4 |
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PLCƣ1 | Yeast two-hybrid | Human | 1-330 | Rat | 780-920 | 12437926 | ||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPC3 |
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PLCƣ1 | Calcium measurement | Activation | 12437926 | |||||||
(:
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