Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK.

Publication ,  Journal Article
Jung, J-H; Pendergast, AM; Zipfel, PA; Traugh, JA
Published in: Biochemistry
January 22, 2008

The tyrosine kinase c-Abl is implicated in a variety of cellular processes that are tightly regulated by c-Abl kinase activity and/or by interactions between c-Abl and other signaling molecules. The interaction of c-Abl with the Abl interactor protein Abi2 is shown to be negatively regulated by phosphorylation of serines 637 and 638. These serines are adjacent to the PxxP motif (PTPPKRS637S638SFR) that binds the SH3 domain of Abi. Phosphorylation of the Abl 593-730 fragment by Pak2 dramatically reduces Abi2 binding ( approximately 90%). Mutation of serines 637-639 to alanine (3A) or aspartate (3D) results in an increased tyrosine kinase activity of c-Abl 3D, and a slight reduction of the activity of the 3A mutant, as compared to wild-type (WT) c-Abl. The interaction between Abi2 and c-Abl 3D is inhibited by 80%, as compared to WT c-Abl or c-Abl 3A. This is accompanied by a 2-fold increase in binding of Crk to c-Abl 3D. The data indicate a molecular mechanism whereby phosphorylation of c-Abl by Pak2 inhibits the interaction between the SH3 domain of Abi2 and the PxxP motif of c-Abl. This phosphorylation enhances the association of c-Abl with the substrate Crk and increases c-Abl-mediated phosphorylation of Crk, thus altering the association of Crk with other signaling molecules.

Duke Scholars

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

January 22, 2008

Volume

47

Issue

3

Start / End Page

1094 / 1104

Location

United States

Related Subject Headings

  • p21-Activated Kinases
  • cdc42 GTP-Binding Protein
  • Transfection
  • Serine
  • Recombinant Proteins
  • Proto-Oncogene Proteins c-crk
  • Proto-Oncogene Proteins c-abl
  • Protein-Tyrosine Kinases
  • Protein Binding
  • Phosphorylation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jung, J.-H., Pendergast, A. M., Zipfel, P. A., & Traugh, J. A. (2008). Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry, 47(3), 1094–1104. https://doi.org/10.1021/bi701533j
Jung, Jin-Hun, Ann Marie Pendergast, Patricia A. Zipfel, and Jolinda A. Traugh. “Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK.Biochemistry 47, no. 3 (January 22, 2008): 1094–1104. https://doi.org/10.1021/bi701533j.
Jung J-H, Pendergast AM, Zipfel PA, Traugh JA. Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry. 2008 Jan 22;47(3):1094–104.
Jung, Jin-Hun, et al. “Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK.Biochemistry, vol. 47, no. 3, Jan. 2008, pp. 1094–104. Pubmed, doi:10.1021/bi701533j.
Jung J-H, Pendergast AM, Zipfel PA, Traugh JA. Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry. 2008 Jan 22;47(3):1094–1104.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

January 22, 2008

Volume

47

Issue

3

Start / End Page

1094 / 1104

Location

United States

Related Subject Headings

  • p21-Activated Kinases
  • cdc42 GTP-Binding Protein
  • Transfection
  • Serine
  • Recombinant Proteins
  • Proto-Oncogene Proteins c-crk
  • Proto-Oncogene Proteins c-abl
  • Protein-Tyrosine Kinases
  • Protein Binding
  • Phosphorylation