Cortactin-Src kinase signaling pathway is involved in N-syndecan-dependent neurite outgrowth.

Abstract

N-syndecan (syndecan-3) was previously isolated as a cell surface receptor for heparin-binding growth-associated molecule (HB-GAM) and suggested to mediate the neurite growth-promoting signal from cell matrix-bound HB-GAM to the cytoskeleton of neurites. However, it is unclear whether N-syndecan would possess independent signaling capacity in neurite growth or in related cell differentiation phenomena. In the present study, we have transfected N18 neuroblastoma cells with a rat N-syndecan cDNA and show that N-syndecan transfection clearly enhances HB-GAM-dependent neurite growth and that the transfected N-syndecan distributes to the growth cones and the filopodia of the neurites. The N-syndecan-dependent neurite outgrowth is inhibited by the tyrosine kinase inhibitors herbimycin A and PP1. Biochemical studies show that a kinase activity, together with its substrate(s), binds specifically to the cytosolic moiety of N-syndecan immobilized to an affinity column. Western blotting reveals both c-Src and Fyn in the active fractions. In addition, cortactin, tubulin, and a 30-kDa protein are identified in the kinase-active fractions that bind to the cytosolic moiety of N-syndecan. Ligation of N-syndecan in the transfected cells by HB-GAM increases phosphorylation of c-Src and cortactin. We suggest that N-syndecan binds a protein complex containing Src family tyrosine kinases and their substrates and that N-syndecan acts as a neurite outgrowth receptor via the Src kinase-cortactin pathway.

• Authors: T Kinnunen, M Kaksonen, J Saarinen, N Kalkkinen, H B Peng, H Rauvala
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 273 Issue 17 Pg. 10702-8 (Apr 24 1998) ISSN: 0021-9258 [Print] United States
• PMID: 9553134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cortactin
• Cttn protein, rat
• DNA, Complementary
• Membrane Glycoproteins
• Microfilament Proteins
• Proteoglycans
• Proto-Oncogene Proteins
• Recombinant Proteins
• Sdc3 protein, rat
• Syndecan-3
• Tubulin
• Fyn protein, rat
• Proto-Oncogene Proteins c-fyn
• Proto-Oncogene Proteins pp60(c-src)
• src-Family Kinases

Topics

• Amino Acid Sequence
• Animals
• Cortactin
• Cytosol (metabolism)
• DNA, Complementary
• Extracellular Matrix (metabolism)
• Membrane Glycoproteins (genetics, metabolism)
• Microfilament Proteins (metabolism)
• Molecular Sequence Data
• Neurites
• Phosphorylation
• Proteoglycans (genetics, metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-fyn
• Proto-Oncogene Proteins pp60(c-src) (metabolism)
• Rats
• Recombinant Proteins (genetics, metabolism)
• Signal Transduction
• Substrate Specificity
• Syndecan-3
• Transfection
• Tubulin (metabolism)
• src-Family Kinases (metabolism)