G-Protein Gα Functions with Abl Kinase to Regulate Actin Cytoskeletal Reorganization

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2017 Oct 29

PMID 29079481

Citations 4

Authors

Limin Wang

Dawei Wang

Bowen Xing

Ying-Cai Tan

Jianyun Huang

Bingqian Liu

Viktoriya Syrovatkina

Cedric Espenel

Geri Kreitzer

Lin Guo

J Jillian Zhang

Xin-Yun Huang

Affiliations

Soon will be listed here.

Abstract

Heterotrimeric G-proteins are essential cellular signal transducers. One of the G-proteins, Gα, is critical for actin cytoskeletal reorganization, cell migration, cell proliferation, and apoptosis. Previously, we have shown that Gα is essential for both G-protein-coupled receptor and receptor tyrosine kinase-induced actin cytoskeletal reorganization such as dynamic dorsal ruffle turnover and cell migration. However, the mechanism by which Gα signals to actin cytoskeletal reorganization is not completely understood. Here we show that Gα directly interacts with Abl tyrosine kinase, which is a critical regulator of actin cytoskeleton. This interaction is critical for Gα-induced dorsal ruffle turnover, endothelial cell remodeling, and cell migration. Our data uncover a new molecular signaling pathway by which Gα controls actin cytoskeletal reorganization.

Citing Articles

G signaling in asthma.

McDuffie E, Panettieri Jr R, Scott C Respir Res. 2024; 25(1):295.

PMID: 39095798 PMC: 11297630. DOI: 10.1186/s12931-024-02920-0.

Gα and Gα: Versatility in Physiology and Pathology.

Guo P, Tai Y, Wang M, Sun H, Zhang L, Wei W Front Cell Dev Biol. 2022; 10:809425.

PMID: 35237598 PMC: 8883321. DOI: 10.3389/fcell.2022.809425.

G-protein Gα functions as a cytoskeletal and mitochondrial regulator to restrain osteoclast function.

Nakano S, Inoue K, Xu C, Deng Z, Syrovatkina V, Vitone G Sci Rep. 2019; 9(1):4236.

PMID: 30862896 PMC: 6414604. DOI: 10.1038/s41598-019-40974-z.

Signaling mechanisms and physiological functions of G-protein Gα in blood vessel formation, bone homeostasis, and cancer.

Syrovatkina V, Huang X Protein Sci. 2018; 28(2):305-312.

PMID: 30345641 PMC: 6319754. DOI: 10.1002/pro.3531.

References

Hernandez S, Krishnaswami M, Miller A, Koleske A . How do Abl family kinases regulate cell shape and movement?. Trends Cell Biol. 2004; 14(1):36-44. DOI: 10.1016/j.tcb.2003.11.003. View

Ma Y, Huang J, Ali S, Lowry W, Huang X . Src tyrosine kinase is a novel direct effector of G proteins. Cell. 2000; 102(5):635-46. DOI: 10.1016/s0092-8674(00)00086-6. View

Schliwa M, Nakamura T, PORTER K, Euteneuer U . A tumor promoter induces rapid and coordinated reorganization of actin and vinculin in cultured cells. J Cell Biol. 1984; 99(3):1045-59. PMC: 2113420. DOI: 10.1083/jcb.99.3.1045. View

Bence K, Ma W, Kozasa T, Huang X . Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit. Nature. 1997; 389(6648):296-9. DOI: 10.1038/38520. View

Sini P, Cannas A, Koleske A, Di Fiore P, Scita G . Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. Nat Cell Biol. 2004; 6(3):268-74. DOI: 10.1038/ncb1096. View

Koleske A, Gifford A, Scott M, Nee M, Bronson R, Miczek K . Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron. 1999; 21(6):1259-72. DOI: 10.1016/s0896-6273(00)80646-7. View

Guo D, Zhang J, Huang X . Stimulation of guanylyl cyclase-D by bicarbonate. Biochemistry. 2009; 48(20):4417-22. PMC: 2684571. DOI: 10.1021/bi900441v. View

Radhika V, Onesime D, Ha J, Dhanasekaran N . Galpha13 stimulates cell migration through cortactin-interacting protein Hax-1. J Biol Chem. 2004; 279(47):49406-13. DOI: 10.1074/jbc.M408836200. View

Korff T, Augustin H . Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation. J Cell Biol. 1998; 143(5):1341-52. PMC: 2133072. DOI: 10.1083/jcb.143.5.1341. View

10.

Shan D, Chen L, Wang D, Tan Y, Gu J, Huang X . The G protein G alpha(13) is required for growth factor-induced cell migration. Dev Cell. 2006; 10(6):707-18. DOI: 10.1016/j.devcel.2006.03.014. View

11.

Fox D, Peifer M . Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell constriction in Drosophila. Development. 2007; 134(3):567-78. DOI: 10.1242/dev.02748. View

12.

Meigs T, Fields T, McKee D, Casey P . Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release. Proc Natl Acad Sci U S A. 2001; 98(2):519-24. PMC: 14619. DOI: 10.1073/pnas.98.2.519. View

13.

Lowry W, Huang J, Ma Y, Ali S, Wang D, Williams D . Csk, a critical link of g protein signals to actin cytoskeletal reorganization. Dev Cell. 2002; 2(6):733-44. DOI: 10.1016/s1534-5807(02)00175-2. View

14.

Mellstrom K, Heldin C, Westermark B . Induction of circular membrane ruffling on human fibroblasts by platelet-derived growth factor. Exp Cell Res. 1988; 177(2):347-59. DOI: 10.1016/0014-4827(88)90468-5. View

15.

Michael M, Vehlow A, Navarro C, Krause M . c-Abl, Lamellipodin, and Ena/VASP proteins cooperate in dorsal ruffling of fibroblasts and axonal morphogenesis. Curr Biol. 2010; 20(9):783-91. PMC: 2946563. DOI: 10.1016/j.cub.2010.03.048. View

16.

Sivaraj K, Takefuji M, Schmidt I, Adams R, Offermanns S, Wettschureck N . G13 controls angiogenesis through regulation of VEGFR-2 expression. Dev Cell. 2013; 25(4):427-34. DOI: 10.1016/j.devcel.2013.04.008. View

17.

Wan Y, Kurosaki T, Huang X . Tyrosine kinases in activation of the MAP kinase cascade by G-protein-coupled receptors. Nature. 1996; 380(6574):541-4. DOI: 10.1038/380541a0. View

18.

Nehls V, Drenckhahn D . A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvasc Res. 1995; 50(3):311-22. DOI: 10.1006/mvre.1995.1061. View

19.

Guo D, Tan Y, Wang D, Madhusoodanan K, Zheng Y, Maack T . A Rac-cGMP signaling pathway. Cell. 2007; 128(2):341-55. PMC: 1965458. DOI: 10.1016/j.cell.2006.11.048. View

20.

Worzfeld T, Wettschureck N, Offermanns S . G(12)/G(13)-mediated signalling in mammalian physiology and disease. Trends Pharmacol Sci. 2008; 29(11):582-9. DOI: 10.1016/j.tips.2008.08.002. View