Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like protein, S(1-5)

T Ozaki1, K Kondo, Y Nakamura

  • 1Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2, Nitona, Chuoh-ku, Chiba, 260, Japan.

Insights

Researchers identified a novel protein, DA41, interacting with the tumor suppressor DAN. This interaction involves the epidermal growth factor-like protein S(1-5) and may regulate cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • A novel protein, DA41, has been identified and shown to associate with the candidate tumor suppressor DAN protein.
  • The interaction partners of DA41 are not fully characterized, limiting understanding of its cellular function.

Purpose of the Study:

  • To identify proteins that interact with DA41.
  • To elucidate the potential role of DA41 in regulating cell growth through its interactions.

Main Methods:

  • Yeast two-hybrid system screening using a truncated DA41 (1-308) as bait.
  • Screening of an adult rat lung cDNA library.
  • Database search to identify the interacting protein.

Main Results:

  • A positive clone, T16, was identified, containing a 1934-nucleotide cDNA encoding a 493-amino acid protein.
  • T16 showed strong sequence similarity to the human epidermal growth factor (EGF)-like protein, S(1-5).
  • The interaction between DA41 and T16 (S(1-5)) was mapped to amino acids 155-232 of DA41.

Conclusions:

  • DA41 interacts with the human epidermal growth factor (EGF)-like protein S(1-5).
  • Given that DAN suppresses and S(1-5) stimulates DNA synthesis, their interaction via DA41 may regulate cell growth.

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.