Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases

Isaac Melamed; Hiren Patel; Chaya Brodie; Erwin W. Gelfand

doi:10.1006/cimm.1998.1402

Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases

Isaac Melamed, Hiren Patel, Chaya Brodie, Erwin W. Gelfand

National Jewish Medical and Research Center

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signalling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions.

Original language	English
Pages (from-to)	83-89
Number of pages	7
Journal	Cellular Immunology
Volume	191
Issue number	2
DOIs	https://doi.org/10.1006/cimm.1998.1402
State	Published - 1 Feb 1999
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported in part by NIH Grants AI-29704 and HL-36577 and Grant 93-00274 from the United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel. Dr. Melamed is a recipient of the Janssen Pharmaceutica Research Award in Allergic Rhinitis from the American Academy of Allergy, Asthma and Immunology. The authors thank Drs. John Cambier and David Kaplan for helpful discussions and Diana Nabighian for preparation of the manuscript.

Funding

This work was supported in part by NIH Grants AI-29704 and HL-36577 and Grant 93-00274 from the United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel. Dr. Melamed is a recipient of the Janssen Pharmaceutica Research Award in Allergic Rhinitis from the American Academy of Allergy, Asthma and Immunology. The authors thank Drs. John Cambier and David Kaplan for helpful discussions and Diana Nabighian for preparation of the manuscript.

Funders	Funder number
National Institutes of Health	93-00274, HL-36577
National Institute of Allergy and Infectious Diseases	R01AI029704
United States-Israel Binational Science Foundation

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10.1006/cimm.1998.1402

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title = "Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases",

abstract = "Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signalling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions.",

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note = "Funding Information: This work was supported in part by NIH Grants AI-29704 and HL-36577 and Grant 93-00274 from the United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel. Dr. Melamed is a recipient of the Janssen Pharmaceutica Research Award in Allergic Rhinitis from the American Academy of Allergy, Asthma and Immunology. The authors thank Drs. John Cambier and David Kaplan for helpful discussions and Diana Nabighian for preparation of the manuscript.",

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Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases

Abstract

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