Receptors for transforming growth factor-beta (TGF-beta) on rat lung fibroblasts have higher affinity for TGF-beta 1 than for TGF-beta 2
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
Most cell types have receptors for transforming growth factor-beta (TGF-beta) and respond similarly to TGF-beta 1 and TGF-beta 2. We have demonstrated the presence of a single class of high-affinity receptors (approximately 10,000 sites/cell) for TGF-beta 1 (Kd = 23 pM) and TGF-beta 2 (Kd = 41 pM) on early-passage rat lung fibroblasts (RLF). Incubation with unlabeled TGF-beta 1 and TGF-beta 2 resulted in concentration-dependent inhibition of binding of 15 pM ({sup 125}I)TGF-beta 1 (ED50, 20 and 28 pM, respectively) and ({sup 125}I)TGF-beta 2 (ED50, 36 and 56 pM, respectively). TGF-beta receptors affinity-cross-linked with 100 pM ({sup 125}I)TGF-beta 1 or ({sup 125}I)TGF-beta 2 were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and exhibited labeled protein bands of 68, 88, and 286 kD. Densitometric analysis of the resulting autoradiograms showed that the different molecular weight TGF-beta binding proteins exhibited separate affinities for the two forms of TGF-beta. Both TGF-beta 1 and TGF-beta 2 altered the morphology and cytoskeleton of RLF in a similar manner, but TGF-beta 1 was more potent than TGF-beta 2 in the inhibition of RLF growth and colony formation, with 50% inhibition by 0.12 pM TGF-beta 1 and 4.4 pM TGF-beta 2. Different affinities for the TGF-beta s may indicate selectivity among the receptor subtypes with regard to the biologic responsiveness of RLF to TGF-beta s. We believe this to be the first demonstration of biologically responsive TGF-beta receptors with different affinities for TGF-beta 1 and TGF-beta 2 on cells derived from normal, nonimmortal RLF. In establishing the basic mechanisms of pulmonary fibrosis, it will be essential to understand the biology and biochemistry of the receptors that may control cell division and production of extracellular matrix components by fibroblasts.
- OSTI ID:
- 5735104
- Journal Information:
- American Journal of Respiratory Cell and Molecular Biology; (USA), Vol. 4:5; ISSN 1044-1549
- Country of Publication:
- United States
- Language:
- English
Similar Records
Binding assay for the solubilized receptors of type beta transforming growth factor: adsorption and removal of free ligand by dextran-coated charcoal
A sensitive equilibrium binding assay for soluble beta-adrenergic receptors
Related Subjects
GROWTH FACTORS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
AFFINITY
AUTORADIOGRAPHY
COLONY FORMATION
ELECTROPHORESIS
FIBROBLASTS
IODINE 125
LUNGS
MOLECULAR WEIGHT
RATS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques