Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth

Tarja Kinnunen, Marko Kaksonen, Juhani Saarinen, Nisse Kalkkinen, H. Benjamin Peng, Heikki Rauvala

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)10702-10708
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number17
DOIs
Publication statusPublished - 24 Apr 1998
Externally publishedYes

Fingerprint

Syndecan-3
Cortactin
src-Family Kinases
Neurites
Neuronal Outgrowth
Phosphotransferases
Growth
Growth Cones
Phosphorylation
Pseudopodia
Cell Surface Receptors
Substrates

Cite this

Kinnunen, Tarja ; Kaksonen, Marko ; Saarinen, Juhani ; Kalkkinen, Nisse ; Peng, H. Benjamin ; Rauvala, Heikki. / Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 17. pp. 10702-10708.
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Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth. / Kinnunen, Tarja; Kaksonen, Marko; Saarinen, Juhani; Kalkkinen, Nisse; Peng, H. Benjamin; Rauvala, Heikki.

In: Journal of Biological Chemistry, Vol. 273, No. 17, 24.04.1998, p. 10702-10708.

Research output: Contribution to journalArticle

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T1 - Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth

AU - Kinnunen, Tarja

AU - Kaksonen, Marko

AU - Saarinen, Juhani

AU - Kalkkinen, Nisse

AU - Peng, H. Benjamin

AU - Rauvala, Heikki

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