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Báo cáo khoa học: WFIKKN1 and WFIKKN2 bind growth factors TGFb1, BMP2 and BMP4 but do not inhibit their signalling activity
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WFIKKN1 and WFIKKN2 are large extracellular multidomain proteins consisting of a WAP domain, a follistatin domain, an immunoglobulin domain, two Kunitz-type protease inhibitor domains and an NTR domain. Recent experiments have shown that both proteins have high affinity for growth and differentiation factor (GDF)8 and GDF11. | IFEBS Journal WFIKKN1 and WFIKKN2 bind growth factors TGFpl BMP2 and BMP4 but do not inhibit their signalling activity Gyorgy Szlama Katalin Kondas Maria Trexler and László Patthy Institute of Enzymology Budapest Hungary Keywords BMP GDF11 GDF8 TGFP WFIKKN Correspondence L. Patthy Institute of Enzymology Budapest Karolina ut 29 Hungary Fax 361 466 5465 Tel 361 209 3537 E-mail patthy@enzim.hu Received 1 June 2010 revised 5 October 2010 accepted 8 October 2010 doi 10.1111 j.1742-4658.2010.07909.x WFIKKN1 and WFIKKN2 are large extracellular multidomain proteins consisting of a WAP domain a follistatin domain an immunoglobulin domain two Kunitz-type protease inhibitor domains and an NTR domain. Recent experiments have shown that both proteins have high affinity for growth and differentiation factor GDF 8 and GDF11. Here we study the interaction of WFIKKN proteins with several additional representatives of the transforming growth factor TGF b family using SPR measurements. Analyses of SPR sensorgrams suggested that in addition to GDF8 and GDF11 both WFIKKN proteins bind TGFb1 bone morphogenetic protein BMP 2 and BMP4 with relatively high affinity Kd 10 6 m . To assess the biological significance of these interactions we studied the effect of WFIKKN proteins on the activity of GDF8 GDF11 TGFp1 BMP2 and BMP4 using reporter assays. These studies revealed that WFIKKN1 and WFIKKN2 inhibited the biological activity of GDF8 and GDF11 in the nanomolar range whereas they did not inhibit the activities of TGFb1 BMP2 and BMP4 even in the micromolar range. Our data indicate that WFIKKN proteins are antagonists of GDF8 and GDF11 but in the case of TGFb1 BMP2 and BMP4 they function as growth factor binding proteins. It is suggested that the physical association of WFIKKN proteins with these growth factors may localize their action and thus help to establish growth factor gradients in the extracellular space. Structured digital abstract A list of the large number of protein-protein .