Models for the activation pathway of epidermal growth factor receptor protein-tyrosine kinase

Conference · Fri Mar 15 04:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5148346

Campion, S R; Niyogi, S K ^[1]

---

1. Oak Ridge National Lab., TN (United States)

Activation of the epidermal growth factor (EGF) receptor's intrinsic protein-tyrosine kinase activity, which occurs upon formation of the receptor-ligand complex, is the critical regulatory event affecting the subsequent EGF-dependent cellular responses leading to DNA synthesis and cell proliferation. The molecular mechanism by which EGF-dependent activation of receptor kinase activity takes place is not clearly understood. In this study, the growth factor-dependent activation of the EGF receptor tyrosine kinase was examined in vitro using detergent-solubilized, partially purified GEF receptors from A5431 human epidermoid carcinoma cells. Evaluation of the cooperativity observed in the EGF-dependent activation of soluble receptor tyrosine kinase would suggest a mechanism requiring the binding of the EGF peptide to both ligand binding sites on a receptor dimer to induce full receptor kinase activity. Equations describing potential cooperative kinase activation pathways have been examined. The theoretical system which best simulates the allosteric regulation observed in the experimental kinase activation data is that describing multiple essential activation. In addition, studies using mutant analogs of the EGF peptide ligand appear to confirm the requirement for an essential conformational change in the receptor-ligand complex to activate the receptor kinase activity. Several mutant growth factor analogues are able to occupy the ligand binding sites on the receptor without inducing the fully active receptor conformation.

• DOE Contract Number: AC05-84OR21400
• OSTI ID: 5148346
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:5
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BODY
CARCINOMAS
CELL PROLIFERATION
DISEASES
DNA REPLICATION
ENZYME ACTIVITY
ENZYMES
EPIDERMIS
EPITHELIUM
EQUATIONS
GROWTH FACTORS
KINETICS
LIGANDS
MAMMALS
MAN
MATHEMATICAL MODELS
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
REACTION KINETICS
RECEPTORS
SKIN
TISSUES
TRANSFERASES
TUMOR CELLS
VERTEBRATES