FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts

Gotoh, Noriko; Laks, Shaked; Nakashima, Misako; Lax, Irit; Schlessinger, Joseph

doi:10.1016/S0014-5793(04)00287-X

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Volume 564, Issue 1 , Pages 14-18, 23 April 2004

FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts

Edited by Veli-Pekka Lehto

Noriko Gotoh
- Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B-204, New Haven, CT 06520, USA
- Present address: Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Shaked Laks
- Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B-204, New Haven, CT 06520, USA
- Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10021, USA
Misako Nakashima
- Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B-204, New Haven, CT 06520, USA
- Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
Irit Lax
- Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B-204, New Haven, CT 06520, USA
Joseph Schlessinger
- Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B-204, New Haven, CT 06520, USA
- Corresponding author. Fax: (1)-203-785 3879

Received 18 February 2004; accepted 24 February 2004.

Abstract

FRS2α and FRS2β, two members of the FRS2 family of docking proteins, become tyrosine phosphorylated in response to fibroblast growth factor (FGF) or nerve growth factor (NGF) stimulation. Tyrosine phosphorylated FRS2α serves as a platform for the recruitment of multiple signaling proteins for activation of the Ras-mitogen-activated protein (MAP) kinase signaling cascade. We report that Frs2α and Frs2β have distinct spatio-temporal expression patterns in mouse embryos. We further show that FRS2β can compensate for the loss of FRS2α for activation of MAP kinase when expressed in fibroblasts from Frs2α^−/− mouse embryos. We propose that the FRS2 family proteins have distinct roles in vivo through activation of common signaling proteins including MAP kinase.

Keywords: Docking protein, FRS2, Fibroblast growth factor, Neurotrophin, Mitogen-activated protein kinase, In situ hybridization

Abbreviations: FGF, fibroblast growth factor, NGF, nerve growth factor, DRG, dorsal root ganglia, VZ, ventricular zone, MEF, mouse embryonic fibroblast