I型转化生长因子β受体的克隆及其对转化生长因子β与II型受体结合的影响。

Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.

作者信息

Ebner R, Chen R H, Shum L, Lawler S, Zioncheck T F, Lee A, Lopez A R, Derynck R

机构信息

Department of Growth and Development, University of California, San Francisco 94143-0640.

出版信息

Science. 1993 May 28;260(5112):1344-8. doi: 10.1126/science.8388127.

DOI:10.1126/science.8388127

PMID:8388127

Abstract

Transforming growth factor-beta (TGF-beta) affects cellular proliferation, differentiation, and interaction with the extracellular matrix primarily through interaction with the type I and type II TGF-beta receptors. The type II receptors for TGF-beta and activin contain putative serine-threonine kinase domains. A murine serine-threonine kinase receptor, Tsk 7L, was cloned that shared a conserved extracellular domain with the type II TGF-beta receptor. Overexpression of Tsk 7L alone did not increase cell surface binding of TGF-beta, but coexpression with the type II TGF-beta receptor caused TGF-beta to bind to Tsk 7L, which had the size of the type I TGF-beta receptor. Overexpression of Tsk 7L inhibited binding of TGF-beta to the type II receptor in a dominant negative fashion. Combinatorial interactions and stoichiometric ratios between the type I and II receptors may therefore determine the extent of TGF-beta binding and the resulting biological activities.

摘要

转化生长因子-β（TGF-β）主要通过与I型和II型TGF-β受体相互作用来影响细胞增殖、分化以及与细胞外基质的相互作用。TGF-β和激活素的II型受体含有假定的丝氨酸-苏氨酸激酶结构域。克隆了一种小鼠丝氨酸-苏氨酸激酶受体Tsk 7L，它与II型TGF-β受体共享一个保守的细胞外结构域。单独过表达Tsk 7L不会增加TGF-β的细胞表面结合，但与II型TGF-β受体共表达会导致TGF-β与Tsk 7L结合，Tsk 7L具有I型TGF-β受体的大小。Tsk 7L的过表达以显性负性方式抑制TGF-β与II型受体的结合。因此，I型和II型受体之间的组合相互作用和化学计量比可能决定TGF-β结合的程度以及由此产生的生物学活性。