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

被引:191
作者
Kinnunen, T
Kaksonen, M
Saarinen, J
Kalkkinen, N
Peng, HB
Rauvala, H
机构
[1] Univ Helsinki, Inst Biotechnol, Mol Neurobiol Lab, Helsinki 00014, Finland
[2] Univ Helsinki, Dept Biosci, Div Biochem, Helsinki 00014, Finland
[3] Univ Helsinki, Prot Chem Lab, Inst Biotechnol, Helsinki 00014, Finland
[4] Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA
关键词
D O I
10.1074/jbc.273.17.10702
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-GARI 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.
引用
收藏
页码:10702 / 10708
页数:7
相关论文
共 56 条
[1]   Substrate recognition by osteoclast precursors induces c-src/microtubule association [J].
AbuAmer, Y ;
Ross, FP ;
Schlesinger, P ;
Tondravi, MM ;
Teitelbaum, SL .
JOURNAL OF CELL BIOLOGY, 1997, 137 (01) :247-258
[2]   SELF-ASSOCIATION OF N-SYNDECAN (SYNDECAN-3) CORE PROTEIN IS MEDIATED BY A NOVEL STRUCTURAL MOTIF IN THE TRANSMEMBRANE DOMAIN AND ECTODOMAIN PLANKING REGION [J].
ASUNDI, VK ;
CAREY, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (44) :26404-26410
[3]   BIOLOGY OF THE SYNDECANS - A FAMILY OF TRANSMEMBRANE HEPARAN-SULFATE PROTEOGLYCANS [J].
BERNFIELD, M ;
KOKENYESI, R ;
KATO, M ;
HINKES, MT ;
SPRING, J ;
GALLO, RL ;
LOSE, EJ .
ANNUAL REVIEW OF CELL BIOLOGY, 1992, 8 :365-393
[4]  
BIXBY JL, 1993, J NEUROSCI, V13, P3421
[5]   An analysis of an axonal gradient of phosphorylated MAP 1B in cultured rat sensory neurons [J].
Bush, MS ;
Goold, RG ;
Moya, F ;
GordonWeeks, PR .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1996, 8 (02) :235-248
[6]   SYNDECAN-1 EXPRESSED IN SCHWANN-CELLS CAUSES MORPHOLOGICAL TRANSFORMATION AND CYTOSKELETAL REORGANIZATION AND ASSOCIATES WITH ACTIN DURING CELL SPREADING [J].
CAREY, DJ ;
STAHL, RC ;
CIZMECISMITH, G ;
ASUNDI, VK .
JOURNAL OF CELL BIOLOGY, 1994, 124 (1-2) :161-170
[7]   MOLECULAR-CLONING AND CHARACTERIZATION OF N-SYNDECAN, A NOVEL TRANSMEMBRANE HEPARAN-SULFATE PROTEOGLYCAN [J].
CAREY, DJ ;
EVANS, DM ;
STAHL, RC ;
ASUNDI, VK ;
CONNER, KJ ;
GARBES, P ;
CIZMECISMITH, G .
JOURNAL OF CELL BIOLOGY, 1992, 117 (01) :191-201
[8]  
Carey DJ, 1997, BIOCHEM J, V327, P1
[9]  
Challacombe JF, 1997, J NEUROSCI, V17, P3085
[10]   The role of an agrin-growth factor interaction in ACh receptor clustering [J].
Daggett, DF ;
Cohen, MW ;
Stone, D ;
Nikolics, K ;
Rauvala, H ;
Peng, HB .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1996, 8 (04) :272-285