Volume 272, Number 4, Issue of January 24, 1997 pp. 2236-2244
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Platelet-derived Growth Factor-stimulated Secretion of Basement Membrane Proteins by Skeletal Muscle Occurs by Tyrosine Kinase-dependent and -independent Pathways

(Received for publication, January 31, 1996, and in revised form, August 15, 1996)

From the Department of Physiological Science, UCLA, Los Angeles, California 90024-1527

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Oguro, T. Sakurai, Y. Fujita, S. Lee, H. Kubota, K. Nagata, and Y. Atomi The molecular chaperone HSP47 rapidly senses gravitational changes in myoblasts Genes Cells, November 1, 2006; 11(11): 1253 - 1265. [Abstract] [Full Text] [PDF]

				M. KJAeR Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading Physiol Rev, April 1, 2004; 84(2): 649 - 698. [Abstract] [Full Text] [PDF]

				L. Rui, S. F. Archer, L. S. Argetsinger, and C. Carter-Su Platelet-derived Growth Factor and Lysophosphatidic Acid Inhibit Growth Hormone Binding and Signaling via a Protein Kinase C-dependent Pathway J. Biol. Chem., January 28, 2000; 275(4): 2885 - 2892. [Abstract] [Full Text] [PDF]

				Z. Yan, D. C. H. Yang, R. Neill, and M. Jett Production of Tumor Necrosis Factor Alpha in Human T Lymphocytes by Staphylococcal Enterotoxin B Correlates with Toxin-Induced Proliferation and Is Regulated through Protein Kinase C Infect. Immun., December 1, 1999; 67(12): 6611 - 6618. [Abstract] [Full Text] [PDF]

				A. Mallat, C. Gallois, J. Tao, A. Habib, J. Maclouf, P. Mavier, A.-M. Preaux, and S. Lotersztajn Platelet-derived Growth Factor-BB and Thrombin Generate Positive and Negative Signals for Human Hepatic Stellate Cell Proliferation. ROLE OF A PROSTAGLANDIN/CYCLIC AMP PATHWAY AND CROSS-TALK WITH ENDOTHELIN RECEPTORS J. Biol. Chem., October 16, 1998; 273(42): 27300 - 27305. [Abstract] [Full Text] [PDF]

				P. Robin, B. Rossignol, and M. N. Raymond PKA inhibitor, H-89, affects the intracellular transit of regulated secretory proteins in rat lacrimal glands Am J Physiol Cell Physiol, January 1, 1998; 274(1): C262 - C271. [Abstract] [Full Text] [PDF]