Antibodies to TIMP Protein Family (Product Review)

Introduction: The tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring proteins that specifically inhibit matrix metalloproteinases and regulate extracellular matrix turnover and tissue remodeling by forming tight-binding inhibitory complexes with the MMPs. Thus, TIMPs maintain the balance between matrix destruction and formation. An imbalance between MMPs and the associated TIMPs may play a significant role in the invasive phenotype of malignant tumors.

The TIMP proteins share several structural features. These include the twelve cysteine residues in conserved regions of the molecule that form six disulfide bonds, essential for the formation of native conformations, and the N-terminal region that is necessary for inhibitory activities. The N-terminus of each TIMP contains a consensus sequence (VIRAK) and each TIMP is translated with a 29 amino acid leader sequence that is cleaved off to produce the mature protein. The C-terminal regions are divergent, which may enhance the selectivity of inhibition and binding efficiency. Although the TIMP proteins share high homology, they may either be secreted extracellularly in soluble form (TIMP-1, TIMP-2 and TIMP-4) or bind to extracellular matrix components (TIMP-3). MMPs and TIMPs can be divided into two groups with respect to gene expression: the majority exhibit inducible expression and a small number are produced constitutively or are expressed at very low levels and are not inducible. Among agents that induce MMP and TIMP production are the inflammatory cytokines TNF alpha and IL1 beta. A marked cell type specificity is a hallmark of both MMP and TIMP gene expression (i.e., a limited number of cell types can be induced to make these proteins).

Antibody Tools for the Detection of Tissue Inhibitors of Metalloproteinases (TIMPs)

Acris Antibodies offers a selection of monoclonal and polyclonal antibodies for immunological detection of various TIMP proteins. These antibodies can be used in applications like immunohistochemistry, immunoprecipitation or Western blotting.

TIMP-1

TIMP-1 was fully sequenced and clone by Carmichael, et al. It is produced and secreted in soluble form by a variety of cell types and is widely distributed throughout the body. It is an extensively glycosylated protein with a molecular mass of 28.5 kDa. TIMP-1 inhibits the active forms of MMPs, and complexes with the proform of MMP9. Like MMP9, TIMP-1 expression is sensitive to many factors. Increased synthesis of TIMP-1 is caused by a wide variety of reagents that include: TGF beta, EGF, PDGF, FGFb, PMA, alltransretinoic acid (RA), IL1 and IL11. The human TIMP-1 gene, about 0.9 kb, has the chromosomal location of Xp11.2311.4.

TIMP-2

TIMP-2 (also called CSC-21K) is a 21 kDa glycoprotein that is expressed by a variety of cell types. It forms a non-covalent, stoichiometric complex with both latent and active MMPs. TIMP-2 shows a preference for MMP-2. TIMP-2 inhibits the proteolytic invasiveness of tumor cells and normal placental trophoblast cells.

TIMP-3

TIMP-3 was first purified from chicken embryo fibroblasts and identified as ChIMP3. The human homologue of TIMP-3, was originally detected as an inducible serum protein in WI-38 fibroblasts. The TIMP-3 localization differs from that of the other three TIMPs, and is thought to be primarily deposited into the extracellular matrix (ECM). TIMP-3 is insoluble, binds to the ECM associated with a variety of cell types, and is widely distributed throughout the body. TIMP-3 shows 30% amino acid homology with TIMP-1 and 38% homology with TIMP-2. TIMP-3 has been shown to promote the detachment of transformed cells from ECM and to accelerate morphological changes associated with cell transformation. Furthermore, up-regulation of TIMP-3 has been associated with a block in the G1 phase of the cell cycle during differentiation of HL-60 leukemia cells. The human TIMP-3 gene has the chromosomal location of 22q12-22q13.

TIMP-4

TIMP-4 was identified by molecular cloning. TIMP-4 shows 37 % amino acid identity with TIMP-1 and 51 % homology with TIMP-2 and TIMP-3. TIMP-4 is secreted extracellularly, predominantly in heart and brain tissue. It may function in a tissue specific fashion in extracellular matrix (ECM) homeostasis. TIMP-4 has a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes suggesting that TIMP-4 may have an important role in inhibiting primary tumor growth and progression. The human TIMP-4 gene has the chromosomal location of 3p25.

Available antibody panel to TIMP

TIMP-1 (TIMP1) antibody, TIMP-2 (TIMP2) antibody, TIMP-3 (TIMP3) antibody, TIMP-4 (TIMP4) antibody