PMID:12885773

Citation	Oak, SA, Zhou, YW and Jarrett, HW (2003) Skeletal muscle signaling pathway through the dystrophin glycoprotein complex and Rac1. J. Biol. Chem. 278:39287-95
Abstract	The dystrophin glycoprotein complex has been proposed to be involved in signal transduction. Here we have shown that laminin binding causes syntrophin to recruit Rac1 from the rabbit skeletal muscle. Laminin-Sepharose and syntrophin-Sepharose bind a protein complex containing Rac1 from the muscle membranes. The presence of heparin, which inhibits laminin interactions, prevents recruitment of Rac1. The dystrophin glycoprotein complex recruits Rac1 via syntrophin through a Grb2.Sos1 complex. A syntrophin antibody also prevents recruitment of Rac1, suggesting that the signaling complex requires syntrophin. PAK1 is in turn bound by Rac1. c-Jun NH2-terminal kinase-p46 is phosphorylated and activated only when laminin is present, and the p54 isoform is activated when laminin is depleted or binding is inhibited with heparin. In the presence of laminin, c-Jun is activated in both skeletal muscle microsomes and in C2C12 myoblasts, and proliferation increases in C2C12 myoblasts. We postulate that this pathway signals muscle homeostasis and hypertrophy.
Links	PubMed Online version:10.1074/jbc.M305551200
Keywords	Adaptor Proteins, Signal Transducing; Animals; Cell Line; Dystrophin/chemistry; Dystrophin/metabolism; Dystrophin-Associated Proteins; Enzyme Activation; GRB2 Adaptor Protein; Glycoproteins/chemistry; Glycoproteins/metabolism; JNK Mitogen-Activated Protein Kinases; Laminin/metabolism; Macromolecular Substances; Membrane Proteins/metabolism; Mice; Mitogen-Activated Protein Kinases/metabolism; Models, Biological; Muscle Proteins/metabolism; Muscle, Skeletal/metabolism; Myoblasts, Skeletal/metabolism; Protein-Serine-Threonine Kinases/metabolism; Proteins/metabolism; Rabbits; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/metabolism; Signal Transduction; p21-Activated Kinases; rac1 GTP-Binding Protein/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RABIT:G1SZI2		GO:0035556: intracellular signal transduction	IDA: Inferred from Direct Assay:	P	Figure 1, 3, 4, 5, 8, & 9 show how PAK1 is part of the signal cascade.	complete CACAO 5926
MOUSE:LAMA1		GO:0006468: phosphorylation	ECO:0000314:		P		Figure 9A.	complete CACAO 5555
MOUSE:LAMA1	involved_in	GO:0006468: protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RABIT:SNTA1		GO:0035556: intracellular signal transduction	ECO:0000314:		P		Figure 1, 3, 4, 5, 8, & 9show how Syntrophin is part of the signal cascade.	complete CACAO 5909
RABIT:SNTA1	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RABIT:DAG1		GO:0035556: intracellular signal transduction	ECO:0000314:		P		Figures 1, 3, 4, 5, 8, & 9 show how beta dystrophin is part of the signal cascade.	complete CACAO 5908
RABIT:DAG1	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RABIT:G1SR27	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RABIT:G1SR27		GO:0035556: intracellular signal transduction	ECO:0000314:		P		Figure 1, 3, 4, 5, 8, & 9 show how Grb2 is part of the signal cascade.	complete CACAO 5910
RABIT:G1TRT1		GO:0035556: intracellular signal transduction	ECO:0000314:		P		Figures 1, 3, 4, 5, 8, & 9 show how Sos1 is part of the signal cascade	complete CACAO 5925
RABIT:G1TRT1	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RABIT:G1SY93		GO:0005886: plasma membrane	ECO:0000314:		C		Figure 1	complete CACAO 6006
RABIT:G1SY93		GO:0035556: intracellular signal transduction	ECO:0000314:		P		Figures 1, 3, 4, 5, 8, & 9 show how Rac1 is part of the signal cascade.	complete CACAO 6007
RABIT:G1SY93	part_of	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
RABIT:G1SY93	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.