Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae.

The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells.

[1]  M. Lisanti,et al.  Molecular and cellular biology of caveolae paradoxes and plasticities. , 1997, Trends in cardiovascular medicine.

[2]  L. Pike,et al.  Localization and Turnover of Phosphatidylinositol 4,5-Bisphosphate in Caveolin-enriched Membrane Domains* , 1996, The Journal of Biological Chemistry.

[3]  C. Mineo,et al.  Clustered folate receptors deliver 5-methyltetrahydrofolate to cytoplasm of MA104 cells , 1996, The Journal of cell biology.

[4]  G. Garcı́a-Cardeña,et al.  Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[5]  L. Pike,et al.  Phosphoinositides and phosphoinositide-utilizing enzymes in detergent-insoluble lipid domains. , 1996, Molecular biology of the cell.

[6]  Richard G. W. Anderson,et al.  Localization of Epidermal Growth Factor-stimulated Ras/Raf-1 Interaction to Caveolae Membrane (*) , 1996, The Journal of Biological Chemistry.

[7]  Richard G. W. Anderson,et al.  Localization of Platelet-derived Growth Factor-stimulated Phosphorylation Cascade to Caveolae (*) , 1996, The Journal of Biological Chemistry.

[8]  John D. Scott,et al.  Molecular Glue: Kinase Anchoring and Scaffold Proteins , 1996, Cell.

[9]  S. Jaken.  Protein kinase C isozymes and substrates. , 1996, Current opinion in cell biology.

[10]  Richard G. W. Anderson,et al.  Acylation Targets Endothelial Nitric-oxide Synthase to Plasmalemmal Caveolae (*) , 1996, The Journal of Biological Chemistry.

[11]  R. G. Anderson,et al.  Hormonal regulation of caveolae internalization , 1995, The Journal of cell biology.

[12]  C. Mineo,et al.  A detergent-free method for purifying caveolae membrane from tissue culture cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Upadhyay,et al.  Platelet-derived growth factor induces apoptosis in growth-arrested murine fibroblasts. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Morrison,et al.  Reversal of Raf-1 activation by purified and membrane-associated protein phosphatases. , 1995, Science.

[15]  D. Mochly‐Rosen.  Localization of protein kinases by anchoring proteins: a theme in signal transduction. , 1995, Science.

[16]  Tony Pawson,et al.  Protein modules and signalling networks , 1995, Nature.

[17]  D. Baltimore,et al.  Modular binding domains in signal transduction proteins , 1995, Cell.

[18]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[19]  I. Herskowitz.  MAP kinase pathways in yeast: For mating and more , 1995, Cell.

[20]  L. Claesson-Welsh,et al.  Platelet-derived growth factor receptor signals. , 1994, The Journal of biological chemistry.

[21]  K. Rothberg,et al.  Purification and characterization of smooth muscle cell caveolae , 1994, The Journal of cell biology.

[22]  R. G. Anderson,et al.  Caveolae: where incoming and outgoing messengers meet. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Y. Nishizuka.  Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. , 1992, Science.

[24]  R. G. Anderson,et al.  Potocytosis: sequestration and transport of small molecules by caveolae. , 1992, Science.

[25]  D. Sanan,et al.  Simultaneous visualization of LDL receptor distribution and clathrin lattices on membranes torn from the upper surface of cultured cells. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[26]  C. Heldin,et al.  Induction of circular membrane ruffling on human fibroblasts by platelet-derived growth factor. , 1988, Experimental cell research.

[27]  M. Waterfield,et al.  Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor ceil , 1988, Nature.

[28]  L. Orci,et al.  Direct visualization of the phosphorylated epidermal growth factor receptor during its internalization in A-431 cells , 1987, The Journal of cell biology.

[29]  L. Tertoolen,et al.  Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts. , 1984, The Journal of biological chemistry.

[30]  Brent H. Cochran,et al.  Molecular cloning of gene sequences regulated by platelet-derived growth factor , 1983, Cell.

[31]  Gary R. Grotendorst,et al.  Platelet-derived growth factor in chemotactic for fibroblasts , 1982, The Journal of cell biology.

[32]  H. Morowitz,et al.  Energy Flow in Biology , 1969 .

[33]  P. Dent,et al.  Preparation and use of semiintact mammalian cells for analysis of signal transduction. , 1995, Methods in enzymology.

[34]  G. Nicolis,et al.  Exploring Complexity: An Introduction , 1989 .

[35]  M. Hosang.  Suramin binds to platelet‐derived growth factor and inhibits its biological activity , 1985, Journal of cellular biochemistry.

[36]  M. Brown,et al.  Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. , 1983, Methods in enzymology.