The platelet-derived growth factor (PDGF) is shown to be chemotactic for monocytes and neutrophils. Maximum monocyte chemotaxis PDGF fully equal that achieved with C5a occurs at congruent 20 ng/ml (congruent 0.7 nM). neutrophil 60% C5A but 1 32 pM). activity of blocked by specific antisera protamine sulfate, a competitive inhibitor binding cell surfaces. In contrast PDGF, epidermal shows no inflammatory cells 0.5-100 ng/ml. high level suggests in addition its role as mitogen smooth muscle...

Human platelets secrete a factor that stimulates cultured human cells to initiate DNA synthesis and divide. This platelet-derived growth (PDGF) has been purified congruent 100,000-fold into two equally active homogeneous fractions, PDGF I (Mr 31,000) II 28,000). The amino acid compositions of each are similar, highly basic, show 18 half-cystine residues. Both glycoproteins, but differ in their carbohydrate compositions. data suggest may be proteolytic cleavage product do not rule out the...

Platelet-derived growth factor (PDGF) stimulates the incorporation of 32P from [gamma-32P]ATP into a Mr approximately 170,000 protein by an endogenous tyrosine-specific kinase in membrane preparations Swiss mouse 3T3 cells. Epidermal (EGF), but not fibroblast (FGF) or insulin, limited similar molecular weight. The ligand concentration required for half-maximal activity (S0.5) PDGF stimulation phosphorylation is 50 ng/ml; saturation achieved at 300 ng/ml. S0.5 ATP 15 microM. Mg2+ Mn2+...

At sites of blood vessel injury, platelets release numerous substances that may have biological activities influencing cellular responses. In this study we examined separately the chemotactic activity for fibroblasts three highly purified proteins obtained from platelet alpha granules: factor 4 (PF4), platelet-derived growth (PDGF), and beta-thromboglobulin (BTG). We observed each these was strongly fibroblasts, with maximum in instance comparable to an optimal concentration control protein,...

Insulin-like growth factor-binding protein 3 (IGFBP-3) has been shown to inhibit cell by IGF-dependent and -independent mechanisms. The putative cell-surface IGFBP-3 receptor that mediates the IGF-independent inhibition not identified. Here we show recombinant human inhibits125I-transforming factor (TGF)-β1 binding type V TGF-β (M r 400,000) in mink lung epithelial cells. We also demonstrate ∼400-kDa125I-IGFBP-3 affinity-labeled is immunoprecipitated specific antiserum receptor. 125I-IGFBP-3...

The near identity of the partial amino acid sequence human platelet-derived growth factor (PDGF) and that predicted for p28 sis , putative transforming protein simian sarcoma virus (SSV), suggests expression a activity may be central transformation by SSV. It is now reported SSV-transformed cells but not control contain identical to PDGF in immunoassay, mitogenic dose response, specific activity. immunoprecipitated antiserum has an apparent molecular weight 20,000, p20 intracellular...

Platelet-derived growth factor (PDGF) is both chemoattractant and mitogenic for stromal cells. Here, we examined the effects of PDGF on collagenase expression by normal human skin fibroblasts. Culturing cells 24 hr in presence at 0-180 ng/ml resulted a dose-dependent, saturable increase activity culture medium that was paralleled equal increases immunoreactive protein, suggesting enhanced synthesis catalytically unaltered enzyme. The specificity this effect demonstrated comparing...

The abbreviations used are: TGF-(3, transforming growth factor ( 3 ; PDGF, human platelet-derived factor; azM, azmacroglobulin; HEPES, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid; SDS, sodium dodecyl sulfate.to identify the binding protein for TGF-P in serum or plasma.In this communication, we report that major of plasma is a,-macroglobulin (a,M) and TGF-P.azMcomplex a latent form TGF-P.

Attempts to measure the platelet-derived growth factor (PDGF) in human plasma resulted discovery of a specific binding protein. The 125I-labeled PDGF (125I-PDGF)-plasma protein complex retained mitogenic activity but lost reactivity against rabbit anti-PDGF antiserum. Copurification and alpha 2-macroglobulin (alpha 2M) plasma, formation between 125I-PDGF purified 2M, comigration 125I-PDGF-plasma 125I-PDGF-alpha 2M NaDodSO4/polyacrylamide gel electrophoresis pore-limiting polyacrylamide...

not exposed to serum; however, at sites of injury, platelets secrete PDGF, and blood coagulation reactions are initiated, providing locally in this instance a serum-like environment for cell growth.Mitogenic responses PDGF mediated through binding the receptor/protein tyrosine kinase stimulates specific target cells by surface receptors which, turn, mediate cascade events that 669 Platelet-derived Growth Factor

The binding of the human platelet-derived growth factor (PDGF) to Swiss mouse 3T3 cells has been investigated.The is specific and reversible.The dissociation constant -0.7 x M with -400,000 sites/cell.Two forms PDGF, PDGF I (Mr = 31,000) II (M, 28,000), previously identified (Deuel, T.

The type V TGF-beta receptor (TbetaR-V)/IGFBP-3 mediates the IGF-independent growth inhibition induced by IGFBP-3. It also inhibitory response to TGF-beta1 in concert with other types, and its loss may contribute malignant phenotype of human carcinoma cells. Here we demonstrate that TbetaR-V is identical LRP-1/alpha2M as shown MALDI-TOF analysis tryptic peptides purified from bovine liver. In addition, 125I-IGFBP-3 affinity-labeled Mv1Lu cells immunoprecipitated antibodies LRP-1 TbetaR-V....

Bovine brain-derived growth factor (BDGF) is very similar to endothelial cell and brainderived acidic fibroblast in terms of PI (5.7) molecular weight (-17,000).BDGF has a wide spectrum specificity, including bovine aorta cells Swiss mouse 3T3 cells.BDGF stimulates the phosphorylation 135-kDa protein plasma membranes cells.The optimal concentration for stimulation close Kd '261-BDGF binding receptor, suggesting that BDGF-stimulated 32P-labeled may be BDGF receptor.The alkaline stability this...

In cells transformed by either v-sis or c-sis, the majority of newly synthesized platelet-derived growth factor (PDGF) receptors fail to reach cell surface and are rapidly degraded. This rapid turnover (t1/2 less than 30 min) appears result from interaction sis gene product with PDGF receptor in endoplasmic reticulum and/or Golgi apparatus during their intracellular routing plasma membrane extracellular compartment. Several lines evidence support this hypothesis. 1) Both 160-kDa precursor...

Six cathepsin D isozymes have been purified from porcine spleen using a large scale purification procedure. Five isozymes, I to V, an identical molecular weight of 50,000 and are similar in specific activity. Isozymes IV contained two polypeptide chains each. The light heavy Mr = 15,000 35,000, respectively. Isozyme V is single polypeptide. the sixth isozyme about 100,000 it has only 5% activity other isozymes. On Ouchterlony immunodiffusion, antiserum formed precipitin lines against...

Clathrin-dependent endocytosis is believed to be involved in TGFbeta-stimulated cellular responses, but the subcellular locus at which TGFbeta induces signaling remains unclear. Here, we demonstrate that inhibitors of clathrin-dependent endocytosis, are known arrest progression coated-pit stages, inhibit internalization cell-surface-bound and promote colocalization accumulation TbetaR-I SARA plasma membrane. These enhance TGFbeta-induced responses (Smad2 phosphorylation/nuclear localization...

The platelet-derived growth factor (PDGF) is the principal mitogen in serum for cultured cells of mesenchymal origin. PDGF also a potent chemotactic protein inflammatory and required wound repair. Because activity levels biological fluids are difficult to measure, we attempted develop radioimmunoassay PDGF. Rabbits were immunized with purified PDGF; antiserum obtained was monospecific immunodiffusion analysis against concentrated platelet lysates, serum, plasma. A developed sensitivity...

High affinity insulin-like growth factor-binding proteins (IGFBP-1 to -6) are a family of structurally homologous that induce cellular responses by factor (IGF)-dependent and -independent mechanisms. The IGFBP-3 receptor, which mediates the IGF-independent inhibitory response, has recently been identified as type V transforming factor-beta receptor (TbetaR-V) (Leal, S. M., Liu, Q. L., Huang, S., J. (1997) Biol. Chem. 272, 20572-20576). To characterize interactions high IGFBPs with TbetaR-V,...

Hypercholesterolemia is a major causative factor for atherosclerotic cardiovascular disease. The molecular mechanisms by which cholesterol initiates and facilitates the process of atherosclerosis are not well understood. Here, we demonstrate that treatment suppresses or attenuates TGF-beta responsiveness in all cell types studied as determined measuring TGF-beta-induced Smad2 phosphorylation nuclear translocation, PAI-1 expression, luciferase reporter gene expression growth inhibition....

Intramolecular pepsinogen activation is inhibited either by pepstatin, a potent pepsin inhibitor, or purified globin from hemoglobin, good substrate. Also, at pH 2 can be bound to pepstatin-Sepharose column and recovered as native zymogen upon elution in 8 buffer. Kinetic studies of the inhibition show that binds intermediate. This interaction gives rise competitive intramolecular activation. The evidence presented this paper suggests converted rapidly acidification intermediate delta. In...

Wound healing consists of re-epithelialization, contraction and formation granulation scar tissue. TGF-b is involved in these events, but its exact roles are not well understood. Here we demonstrate that topical application a synthetic antagonist accelerates re-epithelialization pig burn wounds (100% antagonist-treated vs. approximately 70% control on postburn day 26) reduces wound scarring standard skin burn, excision rabbit wounds. These results support the distinct complex process...