Csk, a critical link of G protein signals to actin cytoskeletal reorganization

William E. Lowry; Jianyun Huang; Yong Chao Ma; Shariq Ali; Dongxia Wang; Daniel M. Williams; Masato Okada; Philip A. Cole; Xin Yun Huang

doi:10.1016/S1534-5807(02)00175-2

Csk, a critical link of G protein signals to actin cytoskeletal reorganization

William E. Lowry, Jianyun Huang, Yong Chao Ma, Shariq Ali, Dongxia Wang, Daniel M. Williams, Masato Okada, Philip A. Cole, Xin Yun Huang^*

^*Corresponding author for this work

Pediatrics

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

69 Scopus citations

Abstract

Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα₁₂, Gα₁₃, and Gα_q)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.

Original language	English (US)
Pages (from-to)	733-744
Number of pages	12
Journal	Developmental Cell
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/S1534-5807(02)00175-2
State	Published - 2002

Funding

We are grateful to Drs. R. Duvoisin, L. Levin, T. Maack, and Y. Zheng for reading the manuscript. We thank Dr. Gary Nolan for the retroviral vectors, Dr. Mike Olson for the plasmid pGEX-KG TAT-C3, and Dr. Wen-Cheng Xiong for GST-Rhotekin. Research in our lab is supported by grants from the NIH, the American Cancer Society, and the Dorothy Rodbell Cohen Foundation for Sarcoma Research. X.-Y.H. is an Established Investigator of the American Heart Association, a Career Scientist of the Irma T. Hirschl Trust, and a Charles H. Leach Foundation Research Scholar.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Molecular Biology
Cell Biology
Developmental Biology

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title = "Csk, a critical link of G protein signals to actin cytoskeletal reorganization",

abstract = "Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα12, Gα13, and Gαq)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.",

author = "Lowry, {William E.} and Jianyun Huang and Ma, {Yong Chao} and Shariq Ali and Dongxia Wang and Williams, {Daniel M.} and Masato Okada and Cole, {Philip A.} and Huang, {Xin Yun}",

note = "Funding Information: We are grateful to Drs. R. Duvoisin, L. Levin, T. Maack, and Y. Zheng for reading the manuscript. We thank Dr. Gary Nolan for the retroviral vectors, Dr. Mike Olson for the plasmid pGEX-KG TAT-C3, and Dr. Wen-Cheng Xiong for GST-Rhotekin. Research in our lab is supported by grants from the NIH, the American Cancer Society, and the Dorothy Rodbell Cohen Foundation for Sarcoma Research. X.-Y.H. is an Established Investigator of the American Heart Association, a Career Scientist of the Irma T. Hirschl Trust, and a Charles H. Leach Foundation Research Scholar.",

year = "2002",

doi = "10.1016/S1534-5807(02)00175-2",

language = "English (US)",

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AU - Lowry, William E.

AU - Huang, Jianyun

AU - Ma, Yong Chao

AU - Ali, Shariq

AU - Wang, Dongxia

AU - Williams, Daniel M.

AU - Okada, Masato

AU - Cole, Philip A.

AU - Huang, Xin Yun

N1 - Funding Information: We are grateful to Drs. R. Duvoisin, L. Levin, T. Maack, and Y. Zheng for reading the manuscript. We thank Dr. Gary Nolan for the retroviral vectors, Dr. Mike Olson for the plasmid pGEX-KG TAT-C3, and Dr. Wen-Cheng Xiong for GST-Rhotekin. Research in our lab is supported by grants from the NIH, the American Cancer Society, and the Dorothy Rodbell Cohen Foundation for Sarcoma Research. X.-Y.H. is an Established Investigator of the American Heart Association, a Career Scientist of the Irma T. Hirschl Trust, and a Charles H. Leach Foundation Research Scholar.

PY - 2002

Y1 - 2002

N2 - Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα12, Gα13, and Gαq)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.

AB - Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα12, Gα13, and Gαq)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.

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Csk, a critical link of G protein signals to actin cytoskeletal reorganization

Abstract

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