Key Specifications Table
|CULT||Human||Recombinant protein expressed in E.coli from the c-sis oncogene.|
|Description||PDGF-BB Protein, human|
|Presentation||Lypholized from 0.1M acetic acid|
|Application||The human PDGF-BB Protein is available in a 10 µg format.|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Material Size||10 µg|
|PDGF-BB (Platelet Derived Growth Factor BB) (human recombinant homodimer) - 1988718||1988718|
|PDGF-BB (Platelet Derived Growth Factor BB) - 2038617||2038617|
|PDGF-BB (Platelet Derived Growth Factor BB) - 2049195||2049195|
|PDGF-BB (Platelet Derived Growth Factor BB) - DAM1564618||DAM1564618|
|PDGF-BB (Platelet Derived Growth Factor BB) - DAM1810787||DAM1810787|
|PDGF-BB (Platelet Derived Growth Factor BB) - JBC1925517||JBC1925517|
|PDGF-BB, human - 15661||15661|
|PDGF-BB, human - 17315||17315|
|PDGF-BB, human - 18403||18403|
|PDGF-BB, human - 19872||19872|
|PDGF-BB, human - 23566||23566|
|Recombinant Human PDGF-BB - 2092640||2092640|
|Recombinant Human -2558377||2558377|
|Recombinant Human -2622605||2622605|
|Recombinant Human -2680750||2680750|
|Recombinant Human -2728394||2728394|
|Recombinant Human -2757176||2757176|
|Recombinant Human PDGF-BB||2470367|
|Recombinant Human PDGF-BB - 2194037||2194037|
|Recombinant Human PDGF-BB - 2266463||2266463|
|Recombinant Human PDGF-BB - 2309022||2309022|
|Reference overview||Application||Pub Med ID|
|Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels |
Suzuki, L. A., et al
Diabetes, 50:851-60 (2001) 2001
|Distinct mechanisms of activation of Stat1 and Stat3 by platelet-derived growth factor receptor in a cell-free system. |
Vignais, M L and Gilman, M
Mol. Cell. Biol., 19: 3727-35 (1999) 1999
Ligand-dependent activation of the platelet-derived growth factor receptor (PDGFR) in fibroblasts in culture leads to the activation of the JAK family of protein-tyrosine kinases and of the transcription factors Stat1 and Stat3. To determine the biochemical mechanism of STAT activation by PDGFR, we devised a cell-free system composed of a membrane fraction from cells overexpressing PDGFR. When supplemented with crude cytosol, the membrane fraction supported PDGF- and ATP-dependent activation of both Stat1 and Stat3. However, the extent of Stat3 activation differed depending on the source of the cytosolic fraction. Using purified recombinant STAT proteins produced in Escherichia coli, we found that Stat1 could be activated by immunopurified PDGFR and showed no additional requirement for membrane- or cytosol-derived proteins. In contrast, activation of Stat3 exhibited a strong requirement for the cytosolic fraction. The activity present in the cytosolic fraction could be depleted with antibodies to JAK proteins. We conclude that the mechanisms of activation of Stat1 and Stat3 by PDGFR are distinct. Stat1 activation appears to result from a direct interaction with the receptor, whereas Stat3 activation additionally requires JAK proteins.
|Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating factor 1/c-fms signaling. |
Fowles, L F, et al.
Mol. Cell. Biol., 18: 5148-56 (1998) 1998
An antibody that specifically recognized phosphothreonine 72 in ets-2 was used to determine the phosphorylation status of endogenous ets-2 in response to colony-stimulating factor 1 (CSF-1)/c-fms signaling. Phosphorylation of ets-2 was detected in primary macrophages, cells that normally express c-fms, and in fibroblasts engineered to express human c-fms. In the former cells, ets-2 was a CSF-1 immediate-early response gene, and phosphorylated ets-2 was detected after 2 to 4 h, coincident with expression of ets-2 protein. In fibroblasts, ets-2 was constitutively expressed and rapidly became phosphorylated in response to CSF-1. In both cell systems, ets-2 phosphorylation was persistent, with maximal phosphorylation detected 8 to 24 h after CSF-1 stimulation, and was correlated with activation of the CSF-1 target urokinase plasminogen activator (uPA) gene. Kinase assays that used recombinant ets-2 protein as a substrate demonstrated that mitogen-activated protein (MAP) kinases p42 and p44 were constitutively activated in both cell types in response to CSF-1. Immune depletion experiments and the use of the MAP kinase kinase inhibitor PD98059 indicate that these two MAP kinases are the major ets-2 kinases activated in response to CSF-1/c-fms signaling. In the macrophage cell line RAW264, conditional expression of raf kinase induced ets-2 expression and phosphorylation, as well as uPA mRNA expression. Transient assays mapped ets/AP-1 response elements as critical for basal and CSF-1-stimulated uPA reporter gene activity. These results indicate that persistent activation of the raf/MAP kinase pathway by CSF-1 is necessary for both ets-2 expression and posttranslational activation in macrophages.
|Platelet-derived growth factor-stimulated secretion of basement membrane proteins by skeletal muscle occurs by tyrosine kinase-dependent and -independent pathways. |
Albrecht, D E and Tidball, J G
J. Biol. Chem., 272: 2236-44 (1997) 1997
The basement membrane of skeletal muscle is produced by the muscle cells it ensheathes and by nonmuscle cells located in the surrounding extracellular matrix. In this study, we have shown that platelet-derived growth factor (PDGF) stimulates secretion of three basement membrane components of skeletal muscle: laminin (70% increase), fibronectin (30%), and type IV collagen (70%). Furthermore, we have found using the signal transduction inhibitors, genistein (tyrosine kinase inhibitor), phorbol 12-myristate 13-acetate (protein kinase C (PKC) inhibitor), thapsigargin (depletes intracellular Ca2+ stores), and H89 (protein kinase A inhibitor), that PDGF-stimulated secretion of these proteins occurs through distinct signaling pathways. Densitometry of Western blots of L6 myoblast supernatant indicates that the PDGF-induced increase in secretion of laminin and type IV collagen is tyrosine kinase-dependent. The increase in type IV collagen secretion also shows dependence on PKC, as well as the release of intracellular Ca2+. Inhibition of either of these pathways reduces the increase in type IV collagen secretion to 20%. In contrast, the PDGF-induced increase in laminin secretion is unaffected by inhibition of either PKC or intracellular Ca2+ release. The increase in fibronectin secretion by PDGF uses yet a third set of signals. PDGF-induced fibronectin secretion is not dependent on tyrosine kinase activity but is dependent on protein kinase A as well as the release of intracellular Ca2+. These divergent signaling pathways provide for independent regulation of basement membrane protein secretion, allowing a muscle cell to modify both the quantity and composition of its basement membrane in response to its environment.
|Galpha16 mimics vasoconstrictor action to induce smooth muscle alpha-actin in vascular smooth muscle cells through a Jun-NH2-terminal kinase-dependent pathway. |
Higashita, R, et al.
J. Biol. Chem., 272: 25845-50 (1997) 1997
Prolonged exposure of vascular smooth muscle cells (VSMC) to vasoconstrictors such as vasopressin or angiotensin II induces hypertrophy and increases expression of muscle-specific genes including smooth muscle alpha-actin (SM-alpha-actin). These vasoconstrictors signal through G-proteins, including members of the Gq family. To further investigate the role of Gq family members, VSMC were transfected with a constitutively active mutant of a Gq family member, Galpha16 (Galpha16Q212L). Stable expression of Galpha16Q212L persistently stimulated phospholipase C, resulting in increased basal levels of inositol phosphates. These cells were hypertrophied and expressed elevated levels of SM-alpha-actin compared with wild-type VSMC or cells transfected with a control plasmid (Neo). SM-alpha-actin promoter activity was markedly increased in cells stably or transiently expressing Galpha16Q212L. Basal c-Jun-NH2-terminal kinase (JNK) activity was increased 3-9-fold in cells stably expressing Galpha16Q212L, while basal activity of the p42/44 mitogen-activated protein kinases (ERKs) was unaffected. Transient expression of a kinase inactive JNK kinase partially inhibited induction of SM-alpha-actin promoter activity in response to vasoconstrictors or expression of Galpha16Q212L. These results indicate that expression of constitutively active Galpha16 in VSMC mimics the effects of vasoconstrictors on hypertrophy and muscle-specific gene expression, and activation of JNK may play a role in these responses.
|The Src SH3 domain is required for DNA synthesis induced by platelet-derived growth factor and epidermal growth factor |
Erpel, T., et al
J Biol Chem, 271:16807-12 (1996) 1996
|Differential translocation of rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor |
Fleming, I. N., et al
J Biol Chem, 271:33067-73 (1996) 1996
|Mechanism of action of platelet-derived growth factor. |
Int. J. Biochem. Cell Biol., 28: 373-85 (1996) 1996
More than 20 years ago, platelet-derived growth factor (PDGF) was identified and later purified. Through recent years of intense research, a large body of information has been collected on how PDGF transduces its biological effects to responding cells. Two homologous receptors, the PDGF alpha- and beta-receptors, have been identified, which are receptor tyrosine kinases. Binding of PDGF leads to activation of the kinase and autophosphorylation. Particularly in the PDGF beta-receptor, a considerable number of autophosphorylation sites have been identified, which allow for physical interaction with signal transduction molecules. The signal transduction molecules are often enzymes, which undergo activity changes in conjunction with binding to the receptor. Other signal transduction molecules function as adaptors, which can couple to subunits equipped with catalytic activity. Through the activity changes of inherent or directly coupled catalytic activities, a signal is propagated, which ultimately results in a cellular response. PDGF is known to induce migration, proliferation and differentiation of different cells types. An array of signal transduction molecules has been shown to interact with the PDGF beta-receptor; several appear to contribute to the generation of the proliferative response, indicating the existence of parallel pathways for this response, which are utilized by many different growth factor receptors. Migration of cells towards PDGF appears to be more strictly dependent on activation of phosphatidylinositol 3' kinase. Interestingly, the PDGF alpha-receptor emits negative signals that inhibit simultaneous positive signals for migration induced by this receptor, or by other receptors, such as the PDGF beta-receptor. Virtually nothing is known about signal transduction initiated by PDGF, which generates differentiation responses. Since PDGF appears to play a role in different physiological and pathological processes, it is important to continue delineation of signal transduction pathways initiated through activation of the PDGF receptors.
|Signal transduction by the platelet-derived growth factor receptor. |
Williams, L T
Science, 243: 1564-70 (1989) 1989
When platelet-derived growth factor (PDGF) binds to its receptor on a quiescent fibroblast or smooth muscle cell, it stimulates a remarkably diverse group of biochemical responses, including changes in ion fluxes, activation of several kinases, alterations in cell shape, increased transcription of a number of genes, and stimulation of enzymes that regulate phospholipid metabolism. These and other reactions culminate, hours later, in DNA replication and cell division. How does the receptor for PDGF recognize and bind its specific ligand and then transduce this signal across the cell membrane via a single membrane-spanning region? Which of the immediate cellular responses are directly involved in the biochemical pathways that lead to DNA synthesis? How does the PDGF receptor trigger a diverse group of responses? Recent studies of the PDGF receptor have provided insight into these issues.