Annotated protein:Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src). Gene symbol: SRC. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9WUD9
antibody wiki:
SynGO gene info:SynGO data @ SRC
Ontology domain:Biological Process
SynGO term:regulation of postsynaptic neurotransmitter receptor activity (GO:0098962)
Synapse type(s):spinal cord, glutamatergic
Annotated paper:Yu XM, et al. "NMDA channel regulation by channel-associated protein tyrosine kinase Src" Science. 1997 Jan 31;275(5300):674-8 PMID:9005855
Figure(s):Fig. 1, Fig. 2, Fig.3, Fig. 4.
Annotation description:Fig. 2. Regulation of NMDA channel gating by endogenous Src.

Literal:
"To determine whether the endogenous kinase was Src itself, we studied the effects
of anti-src1 (Fig. 2, A and B) (n 5 6 patches), which blocks selectively the function
of this kinase (13). Administration of anti-src1 decreased NMDA channel gating with no change in single-channel conductance: Po, mean open time, and burst and
cluster length were significantly reduced, and the open-time distribution was shifted
toward shorter openings and the shut times toward longer closings. The effects
of anti-src1 were prevented when it was incubated with the corresponding immunogen peptide, Src(40-58), for 30 min just before use (n 5 3 patches). Moreover, EPQ(pY)EEIPIA had no effect when applied to patches that had first been treated with anti-src1 (Fig. 2E) (n 5 5 patches). In addition, application of recombinant pp60c-src (1 U/ml; n 5 6 patches) increased Po to 257 +/- 100% of control, mean open time to 125 +/- 10%, burst length to 186 +/- 23%, and cluster length to 220 +/- 33%. These effects were prevented by boiling pp60c-src to heat-inactivate it just before use (n 5 4 patches). Together, these results indicated that NMDA channels were regulated by endogenous Src.

Fig. 3A and B, SRC is associated to NMDA channel proteins.

Literal:
"To determine whether Src and NMDA channels are associated physically, we immunoprecipitated membrane proteins (14) with antibodies specific for the NR1 subunit of NMDA receptors (anti-NR1) or for Src (anti-Src). When we used nondenaturing conditions (15) to solubilize membrane proteins, immunoprecipation with anti-NR1 resulted in coprecipitation of Src (Fig. 3A). Conversely, immunoprecipitation with anti-Src resulted in coprecipitation of NR1 (Fig. 3B). In contrast, the K1 channel protein Kv3.1 (16) was not immunoprecipitated either by anti-Src or anti-NR1, indicating that precipitation of membrane proteins did not occur nonspecifically."

Fig. 4D, synaptic NMDA currents are specifically regulated by endogenous SRC.

Literal:
"In other recordings, addition of anti-src1 or Src(40-58) significantly reduced the NMDA component of the mEPSCs, whereas sSrc(40-58) had no effect (Fig. 4D).
The non-NMDA component of the mEPSCs was unaffected by EPQ(pY)EEIPIA, EPQYEEIPIA, anti-Src1 (n 5 6 cells), Src(40-58) (n 5 7 cells), or sSrc(40-58) (n 5 6 cells). The non-NMDA channels studied in this way were located at the same synapses as the NMDA channels (18); thus, even within the restricted space of a single postsynaptic site, Src appeared to regulate NMDA but not non-NMDA channels."
Evidence tracking, Biological System:Intact tissue
Cultured neurons
Evidence tracking, Protein Targeting:Antagonist / agonist
Evidence tracking, Experiment Assay:Whole-cell patch clamp
Electrophysiology (generic)
IP + WB/MSMS
Annotator(s):Chiara Verpelli (ORCID:0000-0003-2949-9725)
Carlo Sala (ORCID:0000-0003-0662-9523)
Lab:CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
SynGO annotation ID:1784
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology