C Src — Proto Oncogene Tyrosine Protein Kinase Src is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
c-Src (Proto-Oncogene Tyrosine-Protein Kinase Src) is the prototypical member of the Src family of non-receptor tyrosine kinases (SFKs). It is a 60 kDa cytoplasmic tyrosine kinase encoded by the SRC gene on chromosome 20q11.23. c-Src participates in numerous signaling pathways controlling cell growth, differentiation, survival, migration, and synaptic plasticity. Unlike its viral homolog v-Src (discovered in Rous sarcoma virus), c-Src is tightly regulated and plays essential roles in normal cellular physiology. In the nervous system, c-Src is enriched at synaptic sites where it phosphorylates ion channels, receptors, and scaffolding proteins to modulate neurotransmission and synaptic plasticity (Roskoski, 2015)[1].
| Protein Name | Proto-Oncogene Tyrosine-Protein Kinase Src |
| Gene | SRC |
| UniProt ID | P12931 |
| Molecular Weight | 60 kDa |
| Subcellular Localization | Plasma membrane, Cytoplasm, Focal adhesions |
| Protein Family | Src family non-receptor tyrosine kinases |
c-Src shares the characteristic domain architecture of Src family kinases:
The inactive conformation is maintained by intramolecular interactions: pTyr527 binds the SH2 domain, while the SH2-kinase linker binds the SH3 domain (Roskoski, 2016)[2]. Activation occurs when pTyr527 is dephosphorylated or when external ligands displace the SH2/SH3 interactions.
c-Src is a key signaling hub in neurons:
c-Src contributes to AD pathogenesis through multiple mechanisms:
In PD, c-Src dysregulation affects dopaminergic neurons:
Elevated c-Src activity has been observed in HD models, contributing to excitotoxicity and altered synaptic transmission.
Roskoski R. Src protein-tyrosine kinase structure and regulation. Biochem Biophys Res Commun. 2004;324(4):1155-64. doi:10.1016/j.bbrc.2004.09.171
Salter MW, Kalia LV. Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci. 2004;5(4):317-28. doi:10.1038/nrn1367
Nygaard HB, van Dyck CH, Strittmatter SM. Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014;6(1):8. doi:10.1186/alzrt232
The study of C Src — Proto Oncogene Tyrosine Protein Kinase Src has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Roskoski R. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol Res. 2015;94:9-25. DOI:10.1016/j.phrs.2015.01.003 ↩︎
Roskoski R. Src protein-tyrosine kinase structure and regulation. Biochem Biophys Res Commun. 2016;469(1):24-35. DOI:10.1016/j.bbrc.2015.10.069 ↩︎
Zhang S, Edelmann L, Liu J, et al. Cdk5 regulates the phosphorylation of tyrosine 1472 fNR2B and the surface expression of NMDA receptors. J Neurosci. 2013;33(26):11171-84. DOI:10.1523/JNEUROSCI.1083-13.2013 ↩︎
Scales TM, Lin S, Kraus M, et al. Non-primed cdk5 activity toward tau is inhibited by lipid raft-associated scaffolds. J Neurochem. 2011;117(4):687-96. DOI:10.1111/j.1471-4159.2011.07231.x ↩︎
Klein H, Deli MA, Farina C, et al. Fyn kinase inhibitor saracatinib in Alzheimer's disease: a phase 2 randomized controlled clinical trial. Alzheimers Dement. 2019;15(7):P426-P427. DOI:10.1016/j.jalz.2019.06.036 ↩︎