Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain

Exp Cell Res. 1999 Oct 10;252(1):224-35. doi: 10.1006/excr.1999.4609.

Abstract

HEF1, p130(Cas), and Efs define a family of multidomain docking proteins which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. HEF1 function has been specifically implicated in signaling pathways important for cell adhesion and differentiation in lymphoid and epithelial cells. While the SH3 domains and SH2-binding site domains (substrate domains) of HEF1 family proteins are well characterized and binding partners known, to date the highly conserved carboxy-terminal domains of the three proteins have lacked functional definition. In this study, we have determined that the carboxy-terminal domain of HEF1 contains a divergent helix-loop-helix (HLH) motif. This motif mediates HEF1 homodimerization and HEF1 heterodimerization with a recognition specificity similar to that of the transcriptional regulatory HLH proteins Id2, E12, and E47. We had previously demonstrated that the HEF1 carboxy-terminus expressed as a separate domain in yeast reprograms cell division patterns, inducing constitutive pseudohyphal growth. Here we show that pseudohyphal induction by HEF1 requires an intact HLH, further supporting the idea that this motif has an effector activity for HEF1, and implying that HEF1 pseudohyphal activity derives in part from interactions with yeast helix-loop-helix proteins. These combined results provide initial insight into the mode of function of the HEF1 carboxy-terminal domain and suggest that the HEF1 protein may interact with cellular proteins which control differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • Conserved Sequence
  • Crk-Associated Substrate Protein
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Dimerization
  • HeLa Cells
  • Helix-Loop-Helix Motifs / genetics
  • Humans
  • Inhibitor of Differentiation Protein 2
  • Molecular Sequence Data
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Point Mutation
  • Protein Structure, Quaternary
  • Proteins*
  • Repressor Proteins*
  • Retinoblastoma-Like Protein p130
  • Sequence Deletion
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors*

Substances

  • Adaptor Proteins, Signal Transducing
  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • DNA-Binding Proteins
  • EFS protein, human
  • ID2 protein, human
  • Inhibitor of Differentiation Protein 2
  • NEDD9 protein, human
  • Phosphoproteins
  • Proteins
  • Repressor Proteins
  • Retinoblastoma-Like Protein p130
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors