Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6

Han Ie Kim; Jinwon Jung; Eun Saem Lee; Yong Chul Kim; Weontae Lee; Seung Taek Lee

doi:10.1016/j.bbrc.2007.08.055

Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6

Han Ie Kim, Jinwon Jung, Eun Saem Lee, Yong Chul Kim, Weontae Lee, Seung Taek Lee

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

16 Citations (Scopus)

Abstract

PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

Original language	English
Pages (from-to)	829-834
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	362
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2007.08.055
Publication status	Published - 2007 Nov 3

Bibliographical note

Funding Information:
This work was supported by funds from the Korea Science and Engineering Foundation through the Protein Network Research Center at Yonsei University and the National Research Laboratory Program to S.T.L. and W.L., the Seoul Research and Business Development grant (10527) to S.T.L., and the Brain Korea 21 trainee program to S.T.L. and W.L.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2007.08.055

Cite this

@article{87fc5ff1e9324b60a5cefeeb71568f24,

title = "Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6",

abstract = "PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.",

author = "Kim, {Han Ie} and Jinwon Jung and Lee, {Eun Saem} and Kim, {Yong Chul} and Weontae Lee and Lee, {Seung Taek}",

note = "Funding Information: This work was supported by funds from the Korea Science and Engineering Foundation through the Protein Network Research Center at Yonsei University and the National Research Laboratory Program to S.T.L. and W.L., the Seoul Research and Business Development grant (10527) to S.T.L., and the Brain Korea 21 trainee program to S.T.L. and W.L. ",

year = "2007",

month = nov,

day = "3",

doi = "10.1016/j.bbrc.2007.08.055",

language = "English",

volume = "362",

pages = "829--834",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "4",

}

TY - JOUR

T1 - Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6

AU - Kim, Han Ie

AU - Jung, Jinwon

AU - Lee, Eun Saem

AU - Kim, Yong Chul

AU - Lee, Weontae

AU - Lee, Seung Taek

N1 - Funding Information: This work was supported by funds from the Korea Science and Engineering Foundation through the Protein Network Research Center at Yonsei University and the National Research Laboratory Program to S.T.L. and W.L., the Seoul Research and Business Development grant (10527) to S.T.L., and the Brain Korea 21 trainee program to S.T.L. and W.L.

PY - 2007/11/3

Y1 - 2007/11/3

N2 - PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

AB - PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

UR - http://www.scopus.com/inward/record.url?scp=34548544900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548544900&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2007.08.055

DO - 10.1016/j.bbrc.2007.08.055

M3 - Article

C2 - 17822667

AN - SCOPUS:34548544900

SN - 0006-291X

VL - 362

SP - 829

EP - 834

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this