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

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

OSTI ID:5148346

Campion, S R; Niyogi, S K ^[1]

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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-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:5; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

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