Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP2) and activate PKCα, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP2 (PIP2−) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ−) produced a FGF2-specific dominant negative phenotype in endothelial cells as evidenced by the marked decline of their migration and proliferation rates and the impairment of their capacity to form tubes. In both cases, the molecular mechanism was determined to consist of a decrease in the syndecan-4–dependent activation of PKCα. This decrease was caused either by inhibition of FGF2-induced syndecan-4 dephosphorylation in the case of the PDZ− mutation or by disruption of basolateral targeting of syndecan-4 and its associated PDZ-dependent complex in the case of the PIP2− mutation. These results suggest that PKCα activation and PDZ-mediated formation of a serine/threonine phosphatase-containing complex by syndecan-4 are downstream events of FGF2 signaling.
Skip Nav Destination
Article navigation
13 May 2002
Article|
May 13 2002
Fibroblast growth factor–specific modulation of cellular response by syndecan-4
Arie Horowitz,
Arie Horowitz
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Search for other works by this author on:
Eugene Tkachenko,
Eugene Tkachenko
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Search for other works by this author on:
Michael Simons
Michael Simons
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Search for other works by this author on:
Arie Horowitz
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Eugene Tkachenko
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Michael Simons
Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756
Address correspondence to Arie Horowitz, Angiogenesis Research Center and Section of Cardiology, HB-7504, Dept. of Medicine, Dartmouth Medical School, One Medical Center Dr., Lebanon, NH 03756. Tel.: (603) 650-2635. Fax: (603) 653-0510. E-mail: [email protected]
*
Abbreviations used in this paper: EGF, epithelial growth factor; EGFP, enhanced green fluorescent protein; FACS, fluorescence-assisted cell sorting; FGF, fibroblast growth factor; HA, hemagglutinin; HS, heparan sulfate; PDZ, postsynaptic density 95, disk large, zona occludens-1; PIP2, phosphatidylinositol 4,5-bisphosphate; PP1/2A, protein phosphatase type 1/2A; RFPEC, rat fat pad endothelial cell; R-PE, red pycoerythrin.
Received:
December 28 2001
Revision Received:
March 20 2002
Accepted:
March 26 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (4): 715–725.
Article history
Received:
December 28 2001
Revision Received:
March 20 2002
Accepted:
March 26 2002
Citation
Arie Horowitz, Eugene Tkachenko, Michael Simons; Fibroblast growth factor–specific modulation of cellular response by syndecan-4 . J Cell Biol 13 May 2002; 157 (4): 715–725. doi: https://doi.org/10.1083/jcb.200112145
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
Advertisement