Tyrosine kinase inhibitors can differentially inhibit integrin- dependent and CAM-stimulated neurite outgrowth

doi:10.1083/jcb.124.6.1029

This Article

	Full Text (PDF, 1036K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Williams, E. J.
	Articles by Doherty, P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Williams, E. J.
	Articles by Doherty, P.


Social Bookmarking

	What's this?

ARTICLES

Tyrosine kinase inhibitors can differentially inhibit integrin- dependent and CAM-stimulated neurite outgrowth

EJ Williams, FS Walsh and P Doherty
Department of Experimental Pathology, UMDS, Guy's Hospital, London, United Kingdom.

We have used monolayers of parental 3T3 cells and 3T3 cells expressing one of three transfected cell adhesion molecules (CAMs) (NCAM, N- cadherin, and L1) as a culture substrate for rat cerebellar neurons. A number of tyrosine kinase inhibitors have been tested for their ability to inhibit neurite outgrowth over parental 3T3 monolayers which we show to be partly dependent on neuronal integrin receptor function, as compared with neurite outgrowth stimulated by the above three CAMs. Whereas genistein (100 microM), lavendustin A (20 microM), and tyrphostins 34 and 47 (both at 150 microM) had no effect on integrin dependent or CAM stimulated neurite outgrowth, the erbstatin analogue (10-15 micrograms/ml) and tyrphostins 23 and 25 (both at 150 microM) specifically inhibited the response stimulated by all three CAMs. CAM stimulated neurite outgrowth can be accounted for by a G-protein- dependent activation of neuronal calcium channels; experiments with agents that directly activate this pathway localized the erbstatin analogue site of action upstream of the G-protein and calcium channels, whereas tyrphostins have sites of action downstream from calcium channel activation. These data suggest that activation of an erbstatin sensitive tyrosine kinase is an important step upstream of calcium channel activation in the second messenger pathway underlying the neurite outgrowth response stimulated by a variety of CAMs, and that this kinase is not required for integrin-dependent neurite outgrowth.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Sanchez-Heras, E., Howell, F. V., Williams, G., Doherty, P. (2006). The Fibroblast Growth Factor Receptor Acid Box Is Essential for Interactions with N-Cadherin and All of the Major Isoforms of Neural Cell Adhesion Molecule. J. Biol. Chem. 281: 35208-35216 [Abstract] [Full Text]
Shin, D. M., Korada, S., Raballo, R., Shashikant, C. S., Simeone, A., Taylor, J. R., Vaccarino, F. (2004). Loss of Glutamatergic Pyramidal Neurons in Frontal and Temporal Cortex Resulting from Attenuation of FGFR1 Signaling Is Associated with Spontaneous Hyperactivity in Mice. J. Neurosci. 24: 2247-2258 [Abstract] [Full Text]
Williams, G., Williams, E.-J., Doherty, P. (2002). Dimeric Versions of Two Short N-cadherin Binding Motifs (HAVDI and INPISG) Function as N-cadherin Agonists. J. Biol. Chem. 277: 4361-4367 [Abstract] [Full Text]
Suter, D. M., Forscher, P. (2001). Transmission of growth cone traction force through apCAM-cytoskeletal linkages is regulated by Src family tyrosine kinase activity. JCB 155: 427-438 [Abstract] [Full Text]
Jay, D. G. (2001). A Src-astic response to mounting tension. JCB 155: 327-330 [Abstract] [Full Text]
Gogarten, W., Emala, C. W., Lindeman, K. S., Hirshman, C. A. (2001). Oxytocin and Lysophosphatidic Acid Induce Stress Fiber Formation in Human Myometrial Cells via a Pathway Involving Rho-Kinase. Biol. Reprod. 65: 401-406 [Abstract] [Full Text]
Little, E. B., Crossin, K. L., Krushel, L. A., Edelman, G. M., Cunningham, B. A. (2001). A short segment within the cytoplasmic domain of the neural cell adhesion molecule (N-CAM) is essential for N-CAM-induced NF-kappa B activity in astrocytes. Proc. Natl. Acad. Sci. USA 10.1073/pnas.041597098v1 [Abstract] [Full Text]
Jinquan, T., Jing, C., Jacobi, H. H., Reimert, C. M., Millner, A., Quan, S., Hansen, J. B., Dissing, S., Malling, H.-J., Skov, P. S., Poulsen, L. K. (2000). CXCR3 Expression and Activation of Eosinophils: Role of IFN-{gamma}-Inducible Protein-10 and Monokine Induced by IFN-{gamma}. J. Immunol. 165: 1548-1556 [Abstract] [Full Text]
Williams, E., Williams, G., Gour, B. J., Blaschuk, O. W., Doherty, P. (2000). A Novel Family of Cyclic Peptide Antagonists Suggests That N-cadherin Specificity Is Determined by Amino Acids That Flank the HAV Motif. J. Biol. Chem. 275: 4007-4012 [Abstract] [Full Text]
Schaefer, A. W., Kamiguchi, H., Wong, E. V., Beach, C. M., Landreth, G., Lemmon, V. (1999). Activation of the MAPK Signal Cascade by the Neural Cell Adhesion Molecule L1 Requires L1 Internalization. J. Biol. Chem. 274: 37965-37973 [Abstract] [Full Text]
Nieman, M. T., Prudoff, R. S., Johnson, K. R., Wheelock, M. J. (1999). N-Cadherin Promotes Motility in Human Breast Cancer Cells Regardless of Their E-Cadherin Expression. JCB 147: 631-644 [Abstract] [Full Text]
Fang, K., Ionides, E, Oster, G, Nuccitelli, R, Isseroff, R. (1999). Epidermal growth factor receptor relocalization and kinase activity are necessary for directional migration of keratinocytes in DC electric fields. J. Cell Sci. 112: 1967-1978 [Abstract]
Meiri, K. F., Saffell, J. L., Walsh, F. S., Doherty, P. (1998). Neurite Outgrowth Stimulated by Neural Cell Adhesion Molecules Requires Growth-Associated Protein-43 (GAP-43) Function and Is Associated with GAP-43 Phosphorylation in Growth Cones. J. Neurosci. 18: 10429-10437 [Abstract] [Full Text]
Colden-Stanfield, M., Gallin, E. K. (1998). Modulation of K+ currents in monocytes by VCAM-1 and E-selectin on activated human endothelium. Am. J. Physiol. Cell Physiol. 275: C267-C277 [Abstract] [Full Text]
Aplin, A. E., Howe, A., Alahari, S. K., Juliano, R. L. (1998). Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins. Pharmacol. Rev. 50: 197-264 [Abstract] [Full Text]
Kim, T.-A., Lim, J., Ota, S., Raja, S., Rogers, R., Rivnay, B., Avraham, H., Avraham, S. (1998). NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation. JCB 141: 553-566 [Abstract] [Full Text]
Rao, Y., Zipursky, S. L. (1998). Domain requirements for the Dock adapter protein in growth- cone signaling. Proc. Natl. Acad. Sci. USA 95: 2077-2082 [Abstract] [Full Text]
Garver, T. D., Ren, Q., Tuvia, S., Bennett, V. (1997). Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin. JCB 137: 703-714 [Abstract] [Full Text]
Beggs, H. E., Baragona, S. C., Hemperly, J. J., Maness, P. F. (1997). NCAM140 Interacts with the Focal Adhesion Kinase p125fak and the SRC-related Tyrosine Kinase p59fyn. J. Biol. Chem. 272: 8310-8319 [Abstract] [Full Text]
Leventhal, P. S., Feldman, E. L. (1996). Tyrosine Phosphorylation and Enhanced Expression of Paxillin during Neuronal Differentiation in Vitro. J. Biol. Chem. 271: 5957-5960 [Abstract] [Full Text]
Aznavoorian, S., Stracke, M. L., Parsons, J., McClanahan, J., Liotta, L. A. (1996). Integrin alpha(v)beta(3) Mediates Chemotactic and Haptotactic Motility in Human Melanoma Cells through Different Signaling Pathways. J. Biol. Chem. 271: 3247-3254 [Abstract] [Full Text]
Ng-Sikorski, J, Linden, L, Eierman, D, Franzen, L, Molony, L, Andersson, T (1996). Engagement of L-selectin impairs the actin polymerizing capacity of beta 2-integrins on neutrophils. J. Cell Sci. 109: 2361-2369 [Abstract]
Zhao, X., Siu, C.-H. (1995). Colocalization of the Homophilic Binding Site and the Neuritogenic Activity of the Cell Adhesion Molecule L1 to Its Second Ig-like Domain. J. Biol. Chem. 270: 29413-29421 [Abstract] [Full Text]
Stoker, A., Gehrig, B, Haj, F, Bay, B. (1995). Axonal localisation of the CAM-like tyrosine phosphatase CRYP alpha: a signalling molecule of embryonic growth cones. Development 121: 1833-1844 [Abstract]
Williams, E., Furness, J, Walsh, F., Doherty, P (1994). Characterisation of the second messenger pathway underlying neurite outgrowth stimulated by FGF. Development 120: 1685-1693 [Abstract]
Linseman, D. A., Heidenreich, K. A., Fisher, S. K. (2001). Stimulation of M3 Muscarinic Receptors Induces Phosphorylation of the Cdc42 Effector Activated Cdc42Hs-associated Kinase-1 via a Fyn Tyrosine Kinase Signaling Pathway. J. Biol. Chem. 276: 5622-5628 [Abstract] [Full Text]
Little, E. B., Crossin, K. L., Krushel, L. A., Edelman, G. M., Cunningham, B. A. (2001). A short segment within the cytoplasmic domain of the neural cell adhesion molecule (N-CAM) is essential for N-CAM-induced NF-kappa B activity in astrocytes. Proc. Natl. Acad. Sci. USA 98: 2238-2243 [Abstract] [Full Text]