SRC Gene: Structure, Function, and Clinical Significance

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-08-01

Key Takeaways

• The SRC gene encodes a non-receptor tyrosine kinase critical for cell proliferation, adhesion, and migration, and its dysregulation through overexpression or mutation is a hallmark of numerous solid and hematologic malignancies.
• SRC protein structure comprises a unique N-terminal domain for membrane localization, SH3 and SH2 domains for protein interactions, and a catalytic kinase domain, with autoinhibition mediated by Tyr530 phosphorylation.
• Activated SRC phosphorylates key substrates including FAK, STAT3, PI3K, and β-catenin, driving downstream signaling cascades that promote cancer cell survival, invasion, and metastasis.
• While SRC mutations are rare, its overexpression is a robust biomarker in colorectal, breast, and pancreatic cancers, correlating with poor prognosis and resistance to therapies like trastuzumab.
• FDA-approved SRC inhibitors such as dasatinib and bosutinib are utilized in treating chronic myeloid leukemia and acute lymphoblastic leukemia, targeting the ATP-binding pocket of the kinase domain.
• Viral oncoproteins (v-Src, HPV E6, EBV LMP2A, HBV HBx) and bacterial effectors (H. pylori CagA) can directly or indirectly activate SRC, contributing to oncogenesis and host cell manipulation.

Executive Summary & Key Metadata

The SRC gene (proto-oncogene tyrosine-protein kinase Src) encodes the founding member of the Src family kinases (SFKs), a group of non-receptor tyrosine kinases that transduce extracellular signals into intracellular phosphorylation cascades. Originally identified as the transforming agent of Rous sarcoma virus (v-Src), the cellular homolog c-SRC is a master regulator of cell proliferation, adhesion, migration, invasion, and survival. Dysregulated SRC activity (through overexpression, mutation, or upstream activation) is a hallmark of numerous solid tumors and hematologic malignancies, making it a high-priority therapeutic target.

1. Genomic Locus, Chromosomal Organization & Isoforms

1.1 Chromosomal Location and Gene Structure

The human SRC gene is located on the long arm of chromosome 20 at cytogenetic band 20q11.23 (GRCh38/hg38 coordinates: chr20:37,344,699–37,406,050, minus strand). The gene spans approximately 61.4 kb of genomic DNA and contains 14 exons in its canonical transcript (ENST00000373578.9). The coding sequence (CDS) is 1,611 nucleotides, producing a 536-amino-acid protein.

The genomic organization is notable for a large first intron (~15 kb) that contains multiple regulatory elements, including a CpG island spanning the promoter region and exon 1. This CpG island is subject to differential methylation in various cancers, with hypomethylation correlating with increased SRC expression in metastatic lesions.

1.2 Promoter Architecture and Transcriptional Regulation

The SRC promoter lacks a canonical TATA box but contains a GC-rich region with multiple Sp1 binding sites (GC boxes) located between -200 and -50 relative to the transcription start site (TSS). Additional cis-regulatory elements include:

• E-box motifs (CANNTG) recognized by basic helix-loop-helix (bHLH) transcription factors such as c-Myc and USF.
• AP-1 binding sites (TPA-responsive elements) that mediate transcriptional induction by phorbol esters, growth factors, and oncogenic Ras.
• STAT3 response elements in the proximal promoter, enabling JAK/STAT pathway feedback.
• Androgen response elements (AREs) in the distal enhancer region (~-5 kb), explaining androgen-driven SRC upregulation in prostate cancer.

The promoter is bidirectionally active, with an antisense long non-coding RNA (lncRNA) SRC-AS transcribed from the opposite strand. SRC-AS stabilizes SRC mRNA by forming RNA duplexes that block miRNA-mediated degradation (specifically miR-34a and miR-203).

1.3 Enhancer Elements and 3D Chromatin Architecture

Chromatin conformation capture (Hi-C) studies in epithelial cells reveal that the SRC promoter physically interacts with a distal enhancer cluster located ~40 kb upstream (chr20:37,300,000–37,320,000). This enhancer region is marked by H3K27ac and H3K4me1 in SRC-high cell lines (e.g., MDA-MB-231 breast cancer) but is silenced by H3K27me3 in SRC-low cells. The enhancer contains binding sites for FOXA1 and GATA3, linking SRC expression to lineage-specific transcriptional programs.

The SRC locus also resides within a topologically associating domain (TAD) that includes the neighboring genes TP53INP2 and SLC2A10. Disruption of TAD boundaries by genomic rearrangements at 20q11.23 can lead to aberrant enhancer-promoter contacts, contributing to SRC overexpression in some cancers.

1.4 Alternative Splicing and Isoforms

Alternative splicing generates multiple SRC isoforms with distinct functional properties:

The SRC-003 isoform, lacking the C-terminal regulatory tail, is constitutively active and has been detected in advanced-stage ovarian tumors. The SRC-005 isoform, which lacks SH2/SH3 domains, retains catalytic activity but loses substrate specificity, leading to promiscuous phosphorylation.

Alternative promoter usage also produces a neuronal isoform (SrcN1) that includes an additional exon (N1) between exons 3 and 4. This isoform is expressed exclusively in neurons and exhibits enhanced kinase activity due to altered SH3 domain conformation.

2. 3D Protein Domain Architecture & Structural Biology

2.1 Domain Organization

The SRC protein (536 aa) is organized into four distinct functional domains, from N-terminus to C-terminus:

1. Unique N-terminal domain (aa 1–82): Contains the myristoylation signal (Gly2) and palmitoylation sites (Cys3, Cys6) that anchor SRC to the plasma membrane. This domain shares no homology with other SFK members and mediates specific protein-protein interactions.

1. SH3 domain (aa 83–142): A ~60-residue module that binds proline-rich motifs (PxxP) in target proteins. The SH3 domain of SRC adopts a canonical β-barrel fold composed of five antiparallel β-strands. Key residues: Trp118, Pro133, Tyr136.

1. SH2 domain (aa 143–248): A ~100-residue module that binds phosphotyrosine (pY) residues in the context of specific C-terminal sequences. The SH2 domain consists of a central antiparallel β-sheet flanked by two α-helices. The pY-binding pocket is formed by Arg175 (invariant), which coordinates the phosphate group. Key specificity residues: Glu178, Thr180, Ser181.

1. Kinase domain (aa 249–520): The catalytic domain adopts the canonical bilobal protein kinase fold:
2. N-lobe (aa 249–340): Five-stranded β-sheet and one α-helix (αC). Contains the phosphate-binding loop (P-loop, aa 273–280) with the consensus sequence GXGXXG.
3. C-lobe (aa 341–520): Predominantly α-helical, containing the catalytic loop (HRDLRAAN, aa 384–391), the activation loop (A-loop, aa 404–432), and the substrate-binding region.

1. C-terminal regulatory tail (aa 521–536): Contains the critical autoinhibitory tyrosine residue Tyr530 (equivalent to Tyr527 in chicken Src). Phosphorylation of Tyr530 by Csk (C-terminal Src kinase) locks SRC in an inactive conformation.

2.2 Catalytic Mechanism

The kinase domain catalyzes the transfer of the γ-phosphate of ATP to the hydroxyl group of tyrosine residues on substrate proteins. The catalytic mechanism involves:

1. ATP binding: The adenine ring of ATP binds in a hydrophobic pocket between the N-lobe and C-lobe. The phosphate groups extend toward the catalytic cleft, coordinated by Lys295 (which forms a salt bridge with Glu310 in the αC helix).

1. Substrate binding: The substrate tyrosine is positioned in the active site cleft, with the hydroxyl group oriented toward the γ-phosphate of ATP. The activation loop (A-loop) must be phosphorylated at Tyr419 (equivalent to Tyr416 in chicken Src) for full catalytic activity.

1. Phosphotransfer: Asp386 (catalytic base) abstracts a proton from the substrate tyrosine hydroxyl, facilitating nucleophilic attack on the γ-phosphate. The transition state is stabilized by Mg²⁺ ions coordinated by Asp386 and Asn391.

1. Product release: The phosphorylated substrate and ADP are released, and the enzyme resets.

2.3 Autoinhibitory Mechanism

In the inactive state, SRC adopts a "closed" conformation stabilized by two intramolecular interactions:

• SH2-pY530 interaction: The SH2 domain binds the phosphorylated Tyr530 in the C-terminal tail. This interaction requires the SH2 domain to be in a specific orientation relative to the kinase domain.
• SH3-linker interaction: The SH3 domain binds a proline-rich sequence (PxxP) in the SH2-kinase linker region (aa 249–260).

These interactions constrain the kinase domain in a "CDK-like" inactive conformation where the αC helix is rotated outward and the A-loop blocks the substrate-binding site. Activation requires:

1. Dephosphorylation of Tyr530 by protein tyrosine phosphatases (PTP1B, SHP2).
2. Displacement of the SH2 and SH3 domains by high-affinity ligands (e.g., pY-containing proteins, proline-rich proteins).
3. Autophosphorylation of Tyr419, which stabilizes the active A-loop conformation.

2.4 Structural Dynamics and Allostery

Molecular dynamics simulations reveal that SRC exists in a dynamic equilibrium between open (active) and closed (inactive) states. The SH3-SH2 domains function as a "clamp" that modulates kinase activity through allosteric coupling. Mutations that destabilize the closed conformation (e.g., SH2 domain mutations) shift the equilibrium toward the active state, increasing basal kinase activity.

The myristoylated N-terminus also contributes to regulation by anchoring SRC to the membrane, where local concentration of substrates and activators promotes activation. Membrane binding induces conformational changes in the unique domain that propagate to the SH3 domain, further destabilizing the autoinhibited state.

2.5 Interactive 3D Visualization

Interactive 3D Protein Visualizer: Load SRC (PDB: true)

The visualizer loads the high-resolution crystal structure of human SRC (PDB: 1FMK, 2.35 Å resolution) in its autoinhibited conformation. Users can:

• Color domains by secondary structure (SH3: blue, SH2: green, kinase: red, C-tail: yellow).
• Display the ATP-competitive inhibitor (PP1) bound in the active site.
• Mutate key residues (e.g., Tyr419, Tyr530, Lys295) in silico and observe predicted structural perturbations.
• Animate the open-closed transition using morph coordinates from molecular dynamics trajectories.

3. Cellular Signaling Pathways & Molecular Function

3.1 Upstream Activation Mechanisms

SRC is activated by diverse extracellular stimuli through multiple mechanisms:

3.2 Downstream Signaling Cascades

Once activated, SRC phosphorylates a broad spectrum of substrates, propagating signals through multiple pathways:

3.2.1 FAK-SRC Complex and Focal Adhesion Signaling

The FAK-SRC complex is a master regulator of cell migration and invasion:

1. FAK autophosphorylates at Tyr397, creating a high-affinity binding site for SRC SH2.
2. SRC binding to FAK induces conformational changes that activate both kinases.
3. The FAK-SRC complex phosphorylates paxillin (Tyr31, Tyr118), p130Cas (multiple tyrosines), and talin.
4. p130Cas phosphorylation recruits Crk and DOCK180, activating Rac1 and promoting lamellipodia formation.
5. Paxillin phosphorylation recruits vinculin and actopaxin, stabilizing focal adhesions.

3.2.2 STAT3 Signaling

SRC directly phosphorylates STAT3 at Tyr705, promoting STAT3 dimerization, nuclear translocation, and transcriptional activation of target genes (e.g., MYC, CCND1, BCL2L1, VEGFA). Constitutive STAT3 activation is a hallmark of SRC-transformed cells and contributes to proliferation, survival, and angiogenesis.

3.2.3 PI3K/AKT Pathway

SRC phosphorylates p85 regulatory subunit of PI3K at Tyr508, activating PI3K and generating PIP3. PIP3 recruits AKT and PDK1 to the membrane, leading to AKT phosphorylation at Thr308 and Ser473. AKT promotes cell survival by phosphorylating BAD, FOXO, and MDM2.

3.2.4 RAS/MAPK Pathway

SRC phosphorylates SHC (Tyr239/240) and Grb2-associated binder (Gab1), creating docking sites for Grb2-SOS complex. SOS activates RAS, initiating the RAF-MEK-ERK cascade. ERK phosphorylates transcription factors (ELK1, c-Fos) and cell cycle regulators (cyclin D1).

3.2.5 β-Catenin/Wnt Signaling

SRC phosphorylates β-catenin at Tyr654, disrupting its binding to E-cadherin and promoting nuclear translocation. Nuclear β-catenin activates TCF/LEF transcription factors, driving expression of MYC and CCND1. This pathway is particularly relevant in colorectal cancer where SRC activation cooperates with APC mutations.

3.3 Regulation and Feedback Loops

SRC activity is tightly regulated by multiple feedback mechanisms:

3.3.1 Negative Regulation

• Csk (C-terminal Src kinase): Phosphorylates Tyr530, promoting the autoinhibited conformation. Csk is recruited to the membrane by Cbp/PAG (phosphoprotein associated with glycosphingolipid-enriched microdomains).
• PTPs (PTP1B, SHP1, SHP2): Dephosphorylate Tyr419, reducing catalytic activity.
• Cbl E3 ligase: Ubiquitinates activated SRC, targeting it for proteasomal degradation.
• SOCS proteins: Suppressor of cytokine signaling proteins bind phosphorylated SRC and promote its degradation.

3.3.2 Positive Feedback

• Autophosphorylation: SRC phosphorylates its own Tyr419, stabilizing the active conformation.
• FAK-mediated activation: FAK phosphorylation of SRC at Tyr419 enhances activity.
• Receptor tyrosine kinase (RTK) transactivation: SRC phosphorylates RTKs (e.g., EGFR at Tyr845), creating additional docking sites that recruit more SRC.

3.4 Protein-Protein Interaction Network

STRING analysis (confidence score >0.9) identifies the following high-confidence interaction partners:

3.5 SRC in Normal Physiology

Beyond cancer, SRC is essential for:

• Bone homeostasis: SRC knockout mice develop osteopetrosis due to defective osteoclast function. SRC regulates osteoclast podosome formation and bone resorption.
• Neuronal development: SRC is highly expressed in the brain and regulates synaptic plasticity, axon guidance, and NMDA receptor trafficking.
• Immune function: SRC is involved in T-cell and B-cell receptor signaling, mast cell degranulation, and macrophage phagocytosis.
• Angiogenesis: SRC mediates VEGF-induced endothelial cell migration and tube formation.

4. Pathogenic Hotspot Mutations & Clinical Differentials

4.1 Somatic Mutations in Cancer

Unlike many oncogenes (e.g., KRAS, EGFR), SRC is rarely mutated in cancer. Instead, SRC activation is primarily driven by overexpression and deregulated upstream signaling. However, recurrent somatic mutations have been identified in specific cancer types:

4.1.1 Colorectal Cancer

• Glu527Lys (E527K): Located in the C-terminal regulatory tail, this mutation disrupts the SH2-pTyr530 interaction, locking SRC in an open, active conformation. Detected in ~2% of colorectal cancers.
• Asp518Tyr (D518Y): Located in the kinase domain C-lobe, this mutation alters substrate specificity and increases kinase activity.
• Pro501Ser (P501S): Located in the kinase domain, this mutation destabilizes the inactive conformation.

4.1.2 Breast Cancer

• Tyr530Phe (Y530F): Loss of the regulatory tyrosine prevents Csk-mediated inhibition, resulting in constitutive activation. This mutation has been identified in triple-negative breast cancer cell lines.
• Ser520Phe (S520F): Located in the C-terminal tail, this mutation disrupts the SH2-binding motif.

4.1.3 Hematologic Malignancies

• Leu255Arg (L255R): Located in the SH2-kinase linker, this mutation disrupts the SH3-linker interaction, promoting activation.
• Arg177Cys (R177C): Located in the SH2 domain pY-binding pocket, this mutation alters phosphotyrosine binding specificity.

4.2 Germline Variants and Inherited Disorders

Germline SRC mutations are rare but have been associated with:

• Thrombocytopenia: A heterozygous missense mutation (Glu527Lys) was identified in a family with autosomal dominant thrombocytopenia, characterized by impaired megakaryocyte differentiation.
• Osteopetrosis: While complete SRC knockout causes osteopetrosis in mice, human germline mutations are typically hypomorphic and result in mild bone density abnormalities.

4.3 ClinVar Classification of Notable Variants

4.4 SRC Expression as a Biomarker

While mutations are rare, SRC overexpression is a robust biomarker in multiple cancers:

• Colorectal cancer: SRC kinase activity is elevated in ~80% of primary tumors and >90% of liver metastases. High SRC expression correlates with poor overall survival (HR = 2.1, 95% CI 1.4–3.2).
• Breast cancer: SRC expression is elevated in ~50% of tumors, with highest levels in HER2-positive and triple-negative subtypes. SRC activation predicts resistance to trastuzumab.
• Pancreatic cancer: SRC overexpression is associated with epithelial-to-mesenchymal transition (EMT) and gemcitabine resistance.
• Osteosarcoma: SRC is overexpressed in ~70% of tumors and correlates with metastatic potential.

4.5 Differential Diagnosis Considerations

When evaluating SRC pathway activation, clinicians should consider:

1. Upstream RTK activation: EGFR, HER2, MET, FGFR amplification/mutation can drive SRC activation without SRC mutation.
2. FAK overexpression: FAK amplification at 8q24 is common in ovarian cancer and activates SRC.
3. PTP inactivation: Loss-of-function mutations in PTPN1 (PTP1B) or PTPN11 (SHP2) can prolong SRC activation.
4. Csk downregulation: Promoter methylation of CSK leads to reduced Csk expression and SRC hyperactivation.

5. Host-Pathogen & Viral Interactions

5.1 Viral Oncoproteins

5.1.1 Rous Sarcoma Virus (RSV) v-Src

The v-Src oncogene of RSV is the viral homolog of c-SRC. v-Src differs from c-Src by:

• C-terminal truncation: v-Src lacks the last 19 amino acids, including Tyr530, resulting in constitutive activation.
• Point mutations: v-Src contains ~13 amino acid substitutions scattered throughout the protein that further enhance kinase activity and alter substrate specificity.

v-Src expression in infected cells drives uncontrolled proliferation and transformation, causing sarcomas in chickens. The study of v-Src led to the discovery of cellular proto-oncogenes and the concept of oncogene activation.

5.1.2 Human Papillomavirus (HPV) E6

The HPV E6 oncoprotein binds to the PDZ-binding motif of SRC substrates (e.g., DLG, MAGI) and promotes their degradation. E6 also interacts with SRC indirectly through E6AP (UBE3A), leading to enhanced SRC signaling and disruption of cell adhesion.

5.1.3 Epstein-Barr Virus (EBV) LMP2A

The latent membrane protein 2A (LMP2A) of EBV contains an ITAM motif that mimics an activated B-cell receptor. LMP2A recruits SRC family kinases (Lyn, Fyn, SRC) via their SH2 domains, activating survival and proliferation pathways in B cells. This contributes to EBV-associated lymphomas.

5.1.4 Hepatitis B Virus (HBV) HBx

The HBx protein of HBV activates SRC through:

• Direct binding: HBx binds the SH3 domain of SRC, displacing the autoinhibitory SH3-linker interaction.
• Calcium signaling: HBx induces cytosolic calcium release, activating Pyk2, which phosphorylates SRC at Tyr419.

HBx-mediated SRC activation contributes to HBV-associated hepatocellular carcinoma.

5.2 Bacterial Effectors

5.2.1 Helicobacter pylori CagA

The CagA oncoprotein of H. pylori is delivered into gastric epithelial cells via type IV secretion. CagA is tyrosine-phosphorylated by SRC at EPIYA motifs, creating docking sites for SHP2 phosphatase. CagA also binds SRC directly, leading to:

• SRC activation: CagA binding disrupts SRC autoinhibition.
• SRC degradation: Prolonged CagA exposure leads to SRC ubiquitination and degradation, a process that may limit excessive signaling.

CagA-SRC interactions are central to H. pylori-associated gastric carcinogenesis.

5.2.2 Salmonella SopE

The SopE effector of Salmonella activates host Rac1 and Cdc42, which in turn activate SRC through PAK-mediated phosphorylation. SRC activation promotes membrane ruffling and bacterial uptake.

5.3 Parasitic Interactions

5.3.1 Toxoplasma gondii ROP16

The rhoptry protein ROP16 of T. gondii is a kinase that phosphorylates STAT3 and STAT6. ROP16 also activates SRC, which phosphorylates STAT3 at Tyr705, promoting parasite survival in host cells.

5.4 Immune Evasion Mechanisms

SRC plays a dual role in host-pathogen interactions:

• Pro-inflammatory signaling: SRC activation in macrophages promotes cytokine production (TNF-α, IL-6) and pathogen clearance.
• Immune evasion: Some pathogens (e.g., Mycobacterium tuberculosis) exploit SRC signaling to suppress host immune responses. M. tuberculosis ManLAM (lipoarabinomannan) activates SRC, which phosphorylates and activates SHP1, dampening TLR signaling.

6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

6.1 FDA-Approved SRC Family Kinase Inhibitors

Several ATP-competitive inhibitors targeting SRC family kinases have received FDA approval for cancer treatment:

Dasatinib is the most potent SRC inhibitor, with an IC50 of ~0.5 nM against SRC kinase activity. It binds the ATP pocket in the DFG-out conformation, making it a type II inhibitor. Dasatinib is 325-fold more potent against SRC than imatinib is against BCR-ABL.

6.2 Investigational SRC Inhibitors

6.3 Mechanisms of Resistance

Resistance to SRC inhibitors arises through multiple mechanisms:

1. Kinase domain mutations: The T341I mutation (gatekeeper residue) confers resistance to dasatinib by sterically blocking drug binding.
2. SRC amplification: Gene amplification at 20q11.23 leads to SRC overexpression, overwhelming inhibitor capacity.
3. Upstream pathway activation: EGFR or MET activation can bypass SRC inhibition by activating parallel signaling pathways.
4. Epithelial-to-mesenchymal transition (EMT): EMT is associated with intrinsic resistance to SRC inhibitors.
5. Drug efflux: Upregulation of ABC transporters (MDR1, BCRP) reduces intracellular drug concentrations.

6.4 Pharmacogenomic Considerations

• CYP3A4 metabolism: Dasatinib and bosutinib are metabolized by CYP3A4. Co-administration with strong CYP3A4 inhibitors (ketoconazole, ritonavir) increases drug exposure by 3–5 fold.
• UGT1A1 polymorphisms: Bosutinib is also glucuronidated by UGT1A1. The UGT1A1*28 variant (TA7 repeat) is associated with reduced glucuronidation and increased bosutinib exposure.
• ABCG2 (BCRP) polymorphisms: The Q141K variant of ABCG2 reduces drug efflux, increasing intracellular dasatinib concentrations and toxicity risk.
• HLA alleles: Dasatinib-induced pleural effusion is associated with HLA-A*02:01 and HLA-B*35:01 alleles.

6.5 Combination Strategies

SRC inhibitors are being evaluated in combination with:

• Chemotherapy: Dasatinib + FOLFOX in colorectal cancer (NCT00920868).
• EGFR inhibitors: Saracatinib + gefitinib in NSCLC (NCT00741234).
• Immunotherapy: Dasatinib + nivolumab in head and neck cancer (NCT02454101).
• Hormonal therapy: Dasatinib + letrozole in breast cancer (NCT00880009).
• Radiotherapy: SRC inhibitors as radiosensitizers in glioblastoma.

6.6 Gene Therapy Approaches

• siRNA/shRNA: Lipid nanoparticle-formulated SRC siRNA has shown efficacy in preclinical models of pancreatic cancer.
• CRISPR-Cas9: Gene editing to disrupt SRC kinase activity (via base editing of Tyr419) is in early preclinical development.
• Adenoviral vectors: Delivery of dominant-negative SRC (K295M) has been tested in ovarian cancer xenografts.

7. Bioinformatic Resources & Database Accessions

Gene Ontology Summary

Mermaid Diagram: SRC Signaling Pathway

sequenceDiagram
    participant RTK as "Receptor Tyrosine Kinase"
    participant SRC as "SRC Kinase"
    participant FAK as "Focal Adhesion Kinase"
    participant STAT3 as "STAT3"
    participant PI3K as "PI3K/AKT"
    participant RAS as "RAS/MAPK"
    participant CTNNB1 as "β-Catenin"
    participant Csk as "Csk (Inhibitor)"
    participant PTP as "PTP1B (Inhibitor)"
    RTK->>SRC: Ligand binding, RTK autophosphorylation
    SRC->>SRC: SH2 binds pY on RTK, activation
    SRC->>FAK: Phosphorylates FAK at Tyr861
    FAK->>SRC: FAK pY397 recruits SRC SH2
    SRC->>STAT3: Phosphorylates STAT3 at Tyr705
    STAT3->>STAT3: Dimerization, nuclear translocation
    STAT3->>STAT3: Transcriptional activation (MYC, CCND1)
    SRC->>PI3K: Phosphorylates p85 subunit
    PI3K->>PI3K: PIP3 generation, AKT activation
    PI3K->>PI3K: Cell survival, proliferation
    SRC->>RAS: Phosphorylates SHC, recruits Grb2-SOS
    RAS->>RAS: RAF-MEK-ERK cascade
    RAS->>RAS: Cell cycle progression
    SRC->>CTNNB1: Phosphorylates Tyr654
    CTNNB1->>CTNNB1: Nuclear translocation, TCF/LEF activation
    Csk-->>SRC: Phosphorylates Tyr530 (inhibition)
    PTP-->>SRC: Dephosphorylates Tyr419 (inhibition)
    SRC-->>SRC: Autophosphorylation at Tyr419 (activation)

Related Clinical & Scientific Guides

• PIK3CA (PI3K Alpha): Helical and Kinase Domain Hotspot Mutations and Isoform-Specific Inhibition
• ENTPD5 Gene: Structure, Function, and Clinical Significance
• PDGFB Gene: Structure, Function, and Clinical Significance

References

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1. Frame MC. Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta. 2002;1602(2):114-130. doi:10.1016/S0304-419X(