-transparent.png){kind=logo}
Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) possesses both growth-inhibitory and -potentiating effects on cells that are independent of IGF action and are mediated through specific IGFBP-3 binding proteins/receptors located at the cell membrane, cytosol, or nuclear compartments and in the extracellular matrix. We have here characterized transferrin (Tf) as one of these IGFBP-3 binding proteins. Human serum was fractionated over an IGFBP-3 affinity column, and a 70-kDa protein was eluted, sequenced, and identified (through database searching and Western immunoblot) as human Tf. Tf bound IGFBP-3 but had negligible affinity to the other five IGFBPs, and iron-saturated holo-Tf bound IGFBP-3 more avidly than unsaturated Tf. Biosensor interaction analysis confirmed that this interaction is specific and sensitive, with a high association rate similar to IGF-I, and suggested that binding occurs in the vicinity of the IGFBP-3 nuclear localization site. As an independent confirmation of this interaction, using a yeast two-hybrid system, we cloned Tf from a human liver complementary DNA library as an IGFBP-3 protein partner. Tf treatment blocked IGFBP-3-induced cell proliferation in bladder smooth muscle cells, and IGFBP-3-induced apoptosis in prostate cancer cells. In summary, we have employed a combination of techniques to demonstrate that Tf specifically binds IGFBP-3, and we showed that this interaction has important physiological effects on cellular events.
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
December 2001,
FEBS letters,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
January 2003,
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
December 1999,
Nihon rinsho. Japanese journal of clinical medicine,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
August 2005,
Nihon rinsho. Japanese journal of clinical medicine,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
October 2015,
Best practice & research. Clinical endocrinology & metabolism,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
July 1996,
British journal of obstetrics and gynaecology,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
July 1996,
Endocrinology,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
May 2006,
Endocrinology,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
June 2000,
Journal of the American Academy of Dermatology,
S A Weinzimer, and
T B Gibson, and
P F Collett-Solberg, and
A Khare, and
B Liu, and
P Cohen
December 2012,
The Journal of clinical endocrinology and metabolism,
