Mitogen-activated protein (MAP) kinase family members, including extracellular signal–regulated kinase (ERK), c-Jun NH2-terminal kinase ( JNK), and p38 MAP kinase, have been implicated in coupling the B cell antigen receptor (BCR) to transcriptional responses. However, the mechanisms that lead to the activation of these MAP kinase family members have been poorly elucidated. Here we demonstrate that the BCR-induced ERK activation is reduced by loss of Grb2 or expression of a dominant-negative form of Ras, RasN17, whereas this response is not affected by loss of Shc. The inhibition of the ERK response was also observed in phospholipase C (PLC)-γ2–deficient DT40 B cells, and expression of RasN17 in the PLC-γ2–deficient cells completely abrogated the ERK activation. The PLC-γ2 dependency of ERK activation was most likely due to protein kinase C (PKC) activation rather than calcium mobilization, since loss of inositol 1,4,5-trisphosphate receptors did not affect ERK activation. Similar to cooperation of Ras with PKC activation in ERK response, both PLC-γ2–dependent signal and GTPase are required for BCR-induced JNK and p38 responses. JNK response is dependent on Rac1 and calcium mobilization, whereas p38 response requires Rac1 and PKC activation.
Skip Nav Destination
Article navigation
5 October 1998
Article|
October 05 1998
Involvement of Guanosine Triphosphatases and Phospholipase C-γ2 in Extracellular Signal–regulated Kinase, c-Jun NH2-terminal Kinase, and p38 Mitogen-activated Protein Kinase Activation by the B Cell Antigen Receptor
Ari Hashimoto,
Ari Hashimoto
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Hidetaka Okada,
Hidetaka Okada
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Aimin Jiang,
Aimin Jiang
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Mari Kurosaki,
Mari Kurosaki
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Steven Greenberg,
Steven Greenberg
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Edward A. Clark,
Edward A. Clark
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Tomohiro Kurosaki
Tomohiro Kurosaki
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Search for other works by this author on:
Ari Hashimoto
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Hidetaka Okada
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Aimin Jiang
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Mari Kurosaki
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Steven Greenberg
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Edward A. Clark
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Tomohiro Kurosaki
From the *Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan; the ‡Department of Microbiology, University of Washington, Seattle, Washington 98195; and the §Department of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York 10032
Address correspondence to Tomohiro Kurosaki, Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan. Phone: 81-6-993-9445; Fax: 81-6-994-6099; E-mail: [email protected]
Received:
April 30 1998
Revision Received:
July 29 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (7): 1287–1295.
Article history
Received:
April 30 1998
Revision Received:
July 29 1998
Citation
Ari Hashimoto, Hidetaka Okada, Aimin Jiang, Mari Kurosaki, Steven Greenberg, Edward A. Clark, Tomohiro Kurosaki; Involvement of Guanosine Triphosphatases and Phospholipase C-γ2 in Extracellular Signal–regulated Kinase, c-Jun NH2-terminal Kinase, and p38 Mitogen-activated Protein Kinase Activation by the B Cell Antigen Receptor . J Exp Med 5 October 1998; 188 (7): 1287–1295. doi: https://doi.org/10.1084/jem.188.7.1287
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 InstitutionSuggested Content
Email alerts
Advertisement
