The SRC gene encodes a non-receptor tyrosine kinase (often called c-Src) that plays a critical role in regulating cell growth, division, migration, and survival.
Proto-oncogene tyrosine-protein kinase Src.
It was the first proto-oncogene ever discovered.
Viral Homolog: It is closely related to v-src, the cancer-causing gene found in the Rous sarcoma virus.
Structure: Consists of an N-terminal myristoyl group, a unique region, SH4, SH3, SH2 domains, and an SH1 catalytic tyrosine kinase domain.
Activated by autophosphorylation at Tyr-419 (or Tyr-416).
Inhibited by C-terminal Src kinase (CSK) phosphorylation at Tyr-530 (or Tyr-527).
Role in Disease: Overexpression or mutation of c-Src promotes tumor progression, invasion, and metastasis in cancers like colorectal and gastrointestinal stromal tumors, as well as conditions like osteoporosis and thrombocytopenia 6.
Target Therapies: Targeted by kinase inhibitors such as dasatinib, bosutinib, vandetanib, and tirbanibulin.
The human *SRC* gene, located on chromosome 20q11.2, encodes c-SRC, a 60 kDa non-receptor tyrosine kinase that serves as the prototype of the nine-member SRC family of kinases (SFKs)
Discovered as the cellular homolog of the viral oncogene v-*src* from Rous sarcoma virus, it was the first retroviral oncogene counterpart and proto-oncogene identified in vertebrates.
The activation state of SRC depends on specific phosphorylation events:
There is conformational transition between inactive and active SRC kinase
Inactive state: Phosphorylation of tyrosine 530 (Y530) promotes intramolecular binding to its SH2 domain, blocking catalytic kinase activity.
Active state: Dephosphorylation of Y530 releases SH2/SH3-mediated autoinhibition, allowing autophosphorylation at tyrosine 419 (Y419) within the kinase domain for full catalytic activation.
Function and disease implications:
SRC integrates signals from cell-surface receptors—including receptor tyrosine kinases (such as EGFR and HER2), G-protein-coupled receptors, and integrins—to direct cell growth, migration, adhesion, and survival.
Malignancy: Elevated transcription or hyperactivation of SRC occurs in over 50% of colon, liver, lung, breast, and pancreatic cancers, driving tumor progression, angiogenesis, and metastasis via downstream pathways like PI3K-AKT and MAPK-ERK.
Targeted inhibition: Kinase inhibitors with anti-SFK activity (such as dasatinib and bosutinib) are established in oncology, while newer dual-targeting approaches are actively evaluated in solid tumors.
Non-malignant pathology: Germline gain-of-function variants (such as p.E527K) disrupt autoinhibition, leading to thrombocytopenia, bleeding diatheses, and myelofibrosis.
Overall, SRC functions as a central molecular signaling hub in human tissue homeostasis and malignant progression.