Phosphotyrosine-independent Binding of a 62-kDa Protein to the Src Homology 2 (SH2) Domain of P56lck and Its Regulation by Phosphorylation of Ser-59 in the Lck Unique N-terminal Region

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Dec 19

PMID 8618896

Citations 38

Authors

I Park

J Chung

C T WALSH

Y Yun

J L Strominger

J Shin

Affiliations

Soon will be listed here.

Abstract

A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56lck has been identified. The additional presence of the unique N-terminal region of p56lck prevents p62 binding to the SH2 domain. However, phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62. Moreover, p62 is associated with a serine/threonine kinase activity and also binds to ras GTPase-activating protein, a negative regulator of the ras signaling pathway. Thus, phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.

Citing Articles

Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

Yurube T, Buchser W, Zhang Z, Silwal P, Lotze M, Kang J JOR Spine. 2024; 7(1):e1303.

PMID: 38222800 PMC: 10782056. DOI: 10.1002/jsp2.1303.

The versatile defender: exploring the multifaceted role of p62 in intracellular bacterial infection.

Zhou Y, Hua S, Song L Front Cell Infect Microbiol. 2023; 13:1180708.

PMID: 37216179 PMC: 10196109. DOI: 10.3389/fcimb.2023.1180708.

Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy.

Yurube T, Takeoka Y, Kanda Y, Kuroda R, Kakutani K N Am Spine Soc J. 2023; 14:100210.

PMID: 37090223 PMC: 10113901. DOI: 10.1016/j.xnsj.2023.100210.

The Role of VCP Mutations in the Spectrum of Amyotrophic Lateral Sclerosis-Frontotemporal Dementia.

Scarian E, Fiamingo G, Diamanti L, Palmieri I, Gagliardi S, Pansarasa O Front Neurol. 2022; 13:841394.

PMID: 35273561 PMC: 8902152. DOI: 10.3389/fneur.2022.841394.

Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).

Tang J, Li Y, Xia S, Li J, Yang Q, Ding K Int J Oncol. 2021; 59(4).

PMID: 34414460 PMC: 8425587. DOI: 10.3892/ijo.2021.5257.

References

Chan A, Desai D, Weiss A . The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu Rev Immunol. 1994; 12:555-92. DOI: 10.1146/annurev.iy.12.040194.003011. View

Eck M, Shoelson S, Harrison S . Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature. 1993; 362(6415):87-91. DOI: 10.1038/362087a0. View

Xu H, Littman D . A kinase-independent function of Lck in potentiating antigen-specific T cell activation. Cell. 1993; 74(4):633-43. DOI: 10.1016/0092-8674(93)90511-n. View

Duplay P, Thome M, Herve F, Acuto O . p56lck interacts via its src homology 2 domain with the ZAP-70 kinase. J Exp Med. 1994; 179(4):1163-72. PMC: 2191435. DOI: 10.1084/jem.179.4.1163. View

Shin J, Doyle C, Yang Z, Kappes D, Strominger J . Structural features of the cytoplasmic region of CD4 required for internalization. EMBO J. 1990; 9(2):425-34. PMC: 551683. DOI: 10.1002/j.1460-2075.1990.tb08127.x. View

Malek S, Desiderio S . A cyclin-dependent kinase homologue, p130PITSLRE is a phosphotyrosine-independent SH2 ligand. J Biol Chem. 1994; 269(52):33009-20. View

Autero M, Saharinen J, Pessa-Morikawa T, Soula-Rothhut M, Oetken C, Gassmann M . Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase. Mol Cell Biol. 1994; 14(2):1308-21. PMC: 358486. DOI: 10.1128/mcb.14.2.1308-1321.1994. View

Wong G, Muller O, Clark R, Conroy L, Moran M, Polakis P . Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62. Cell. 1992; 69(3):551-8. DOI: 10.1016/0092-8674(92)90455-l. View

Joung I, Kim T, Stolz L, Payne G, Winkler D, WALSH C . Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain. Proc Natl Acad Sci U S A. 1995; 92(13):5778-82. PMC: 41584. DOI: 10.1073/pnas.92.13.5778. View

10.

Payne G, Shoelson S, Gish G, Pawson T, WALSH C . Kinetics of p56lck and p60src Src homology 2 domain binding to tyrosine-phosphorylated peptides determined by a competition assay or surface plasmon resonance. Proc Natl Acad Sci U S A. 1993; 90(11):4902-6. PMC: 46621. DOI: 10.1073/pnas.90.11.4902. View

11.

Winkler D, Park I, Kim T, PAYNE N, WALSH C, Strominger J . Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck. Proc Natl Acad Sci U S A. 1993; 90(11):5176-80. PMC: 46678. DOI: 10.1073/pnas.90.11.5176. View

12.

Kunkel T . Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985; 82(2):488-92. PMC: 397064. DOI: 10.1073/pnas.82.2.488. View

13.

Cooper J, Howell B . The when and how of Src regulation. Cell. 1993; 73(6):1051-4. DOI: 10.1016/0092-8674(93)90634-3. View

14.

Weber J, Bell G, Han M, Pawson T, Imboden J . Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor. J Exp Med. 1992; 176(2):373-9. PMC: 2119313. DOI: 10.1084/jem.176.2.373. View

15.

Cleghon V, Morrison D . Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner. J Biol Chem. 1994; 269(26):17749-55. View

16.

Muller A, Pendergast A, Havlik M, Puil L, Pawson T, Witte O . A limited set of SH2 domains binds BCR through a high-affinity phosphotyrosine-independent interaction. Mol Cell Biol. 1992; 12(11):5087-93. PMC: 360442. DOI: 10.1128/mcb.12.11.5087-5093.1992. View

17.

Fantl W, Escobedo J, Martin G, Turck C, del Rosario M, McCormick F . Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways. Cell. 1992; 69(3):413-23. DOI: 10.1016/0092-8674(92)90444-h. View

18.

Chen C, Okayama H . High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987; 7(8):2745-52. PMC: 367891. DOI: 10.1128/mcb.7.8.2745-2752.1987. View

19.

Weiss A, Littman D . Signal transduction by lymphocyte antigen receptors. Cell. 1994; 76(2):263-74. DOI: 10.1016/0092-8674(94)90334-4. View

20.

Mayer B, Jackson P, Van Etten R, Baltimore D . Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Mol Cell Biol. 1992; 12(2):609-18. PMC: 364250. DOI: 10.1128/mcb.12.2.609-618.1992. View