CRK Human
Description
Molecular Structure and Isoforms
CRK Human exists in two primary isoforms due to alternative splicing:
Both isoforms belong to a conserved adaptor protein family that lacks enzymatic activity but mediates protein-protein interactions through SH2 (binds phosphotyrosine residues) and SH3 (binds proline-rich motifs) domains . CrkL, a paralog encoded by the CRKL gene on chromosome 22, shares 57% amino acid identity with CrkII and often functions redundantly in signaling .
Biological Functions and Signaling Pathways
CRK Human integrates signals from receptor tyrosine kinases (RTKs) and cytokine receptors:
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Reelin Pathway: Participates in neuronal migration via DAB1 phosphorylation downstream of Reelin receptors .
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Oncogenic Signaling:
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Immune Regulation: Modulates NK cell cytotoxicity and T/B cell activation through interactions with DOCK1/4 and C3G .
Role in Human Cancer
CRK overexpression correlates with aggressive tumor phenotypes:
Knockdown of CRK/CrkL reduces tumor growth in preclinical models by up to 70% . Conversely, ectopic CrkI expression in fibroblasts induces anchorage-independent growth and xenograft tumorigenesis .
Recombinant CRK Human Protein
Recombinant CRK (produced in E. coli) is used for biochemical studies:
| Parameter | Specification |
|---|---|
| Molecular Weight | 25 kDa (224 amino acids, residues 1-204 + 20-aa His tag) |
| Purity | >95% (SDS-PAGE) |
| Buffer | 20 mM Tris-HCl (pH 8.0), 10% glycerol |
| Stability | 2–4 weeks at 4°C; long-term storage at -20°C with carrier protein (e.g., 0.1% HSA) |
This reagent facilitates studies on CRK’s SH2/SH3 domain interactions and phosphorylation-dependent signaling .
Therapeutic Targeting
CRK/CrkL are emerging targets in oncology:
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Gene Silencing: siRNA against Crk suppresses glioma xenograft growth by 60% .
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Small-Molecule Inhibitors: Compounds disrupting SH2-phosphotyrosine binding (e.g., bisphosphorylated peptides) are under investigation .
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Combination Therapy: Crk inhibition synergizes with Src or MET inhibitors in preclinical models .
Disease Associations
Beyond cancer, CRK dysregulation is implicated in:
Product Specs
Product Science Overview
The CRKL gene was first identified as an oncogene product of the avian sarcoma virus CT10 . The protein encoded by this gene is structurally similar to the v-Crk protein, which consists of a viral Gag portion fused with a Src homology domain . The human recombinant version of CRKL retains these critical domains, enabling it to interact with various signaling molecules within the cell.
CRKL is involved in multiple cellular signaling pathways. It acts as an adaptor protein, facilitating the interaction between different signaling molecules. This protein is known to be upregulated in several types of human cancers, including leukemia, cervical cancer, and hepatocellular carcinoma . Its role in cancer progression is attributed to its ability to regulate alternative splicing of cancer-related genes and its involvement in key signaling pathways such as DNA repair, G2/M mitotic cell cycle, and GnRH signaling .
CRKL exerts its effects through its SH2 and SH3 domains, which allow it to bind to phosphorylated tyrosine residues on other proteins. This binding facilitates the formation of protein complexes that are essential for signal transduction. In cancer cells, CRKL has been shown to regulate the expression of genes involved in cell proliferation and invasion, contributing to tumor growth and metastasis .
The overexpression of CRKL in various cancers makes it a potential target for therapeutic interventions. Understanding the regulatory mechanisms of CRKL and its role in cancer progression can provide insights into developing targeted therapies for cancer treatment. Additionally, the identification of the ETV6-miR-429-CRKL regulatory circuitry in hepatocellular carcinoma highlights the complex interactions between different signaling molecules and their impact on cancer aggressiveness .
