Src (rat, UniProtKB:Q9WUD9) - manual literature synthesis

No deep-research provider was available for this session; this synthesis was written by
hand from the cached publications in publications/ and the UniProt record
(Src-uniprot.txt). Quotes are verbatim from those sources.

Identity and domain architecture

• Rat proto-oncogene tyrosine-protein kinase Src (c-Src, pp60c-src), 536 aa, GeneID 83805,
  RGD:620795. N-myristoylated Gly2; SH3 (84-145), SH2 (151-248) and tyrosine kinase domain
  (270-523), proton acceptor Asp389, activating autophosphorylation at Tyr419 and inhibitory
  CSK site Tyr530 [UniProtKB:Q9WUD9].
• UniProt: "Non-receptor protein tyrosine kinase which is activated following engagement of
  many different classes of cellular receptors including immune response receptors,
  integrins and other adhesion receptors, receptor protein tyrosine kinases, G
  protein-coupled receptors as well as cytokine receptors." [UniProtKB:Q9WUD9]
• Three isoforms: c-Src, neuron-specific N1-Src (6-aa SH3 n-src loop insert) and N2-Src
  (17-aa insert). PMID:26026271 N1-Src drives neurite elongation PMID:28220894.

Catalytic activity (rat-specific evidence)

• GPCR to MAP kinase via Pyk2 in PC12 cells: PMID:8849729
• Gastrin/progastrin-induced c-Src kinase activity in intestinal epithelial cells (PMID:12488346).
• ATP-induced Src autophosphorylation in brain mitochondria PMID:18583343.

Neuronal / synaptic role (rat)

• Src is an NMDA receptor-associated kinase that up-regulates NMDA channel activity:
  [PMID:9005855 "the endogenous tyrosine kinase Src was shown to regulate the activity of
  NMDA channels"; "Src coprecipitated with NMDA receptor proteins"].
• Anchoring via ND2: PMID:15069201
• PSD-95 binding: PMID:14529711
• Ischemia: NR2A-PSD-95-Src module, Pyk2-facilitated NR2A phosphorylation
  (PMID:11478920, PMID:12618293, PMID:15814199, PMID:20197063).
• Learning correlates with Src up-regulation in hippocampal synaptic membranes
  (PMID:10884433, expression only).

Vascular smooth muscle / GPCR signalling (rat)

• PMID:7586216
• PMID:8626602
• PMID:9227431.

Growth factor signalling, adhesion, other contexts

• PDGF in mesangial cells: PMID:16530387.
• Adhesion: r-PTPeta activates c-Src by dephosphorylating Tyr529 and increases adhesion
  (PMID:15735685).
• Caveolae endocytosis/transcytosis: PMID:15007081.
• Osteoclastic bone resorption (pharmacological, PMID:8514886).
• Mitochondria: rat brain mitochondria contain Src (PMID:12007793, PMID:18583343,
  PMID:21063895).
• Testis: Src in Sertoli cells, spermatids, adherens junction complexes (PMID:7530000,
  PMID:10698670, PMID:15389520, PMID:15591141) - largely expression/correlation.
• v-Src in Rat-1 fibroblasts depends on annexin 2 for membrane targeting and transformation:
  PMID:19193640
  This concerns the viral oncoprotein, not rat c-Src, though the authors note c-Src-GFP behaved
  similarly (data not shown).

Caveats

Most rat papers use pharmacological inhibitors (PP1, PP2, herbimycin A) or antibodies that do
not distinguish Src from other Src-family kinases; many GOA rows are IEP rows reflecting
Src activation or expression after a stimulus rather than a demonstrated role.