KOSEN 한인과학기술자네트워크

주요연구방향 (Research Focus)

본 연구실은 동물의 영양 및 생리적 대사작용에 관여하는 내분비의 조절 및 발현과 세포내 신호전달체계에 대해 연구하는 실험실이다. 내분비세포에서 분비되는 물질을 호르몬이라 부르며, 이 호르몬이 혈관을 통해 운송되에 세포막 또는 세포내의 수용체에 결합하여 세포내 신호전달을 야기시키고 유전자를 발현시킨다. 각각의 호르몬에 대한 이러한 특이적인 작용에 의해 동물체내의 대사작용 뿐만 아니라, 성장, 분만, 및 노화 등 일련의 생명현상이 조절된다. 현재 진행중인 연구는 1) 성장호르몬의 자극에 의해 간에서 분비되는 Insulin like-growth factor-I (IGF-I)의 결합체의 하나인 acid labile subunit (ALS)라 불리우는 단백질의 동정 및 발현 조절,  2) 이중 형질전환 생쥐 (ALS ´ IGF-II)을 이용한 IGF-II의 성장 및 대사작용, 3) 지방세포에서 분비되는 adiponectin의 발현 조절, 4) 유방암의 발생에 영향하는 대사인자 및 내분비 작용의 규명 등을 수행하고 있다.

My research program focuses on endocrine regulation of metabolism and physiology. Hormones, which belong to a class of regulatory molecules synthesized in special endocrine cells. They enter a local blood vessel and circulate to their target cells. Hormones act by binding to specific receptors on the target-cell surface or within the cell. The consequence is a signal cascade of intracellular interactions, which amplifies the original stimulus and leads ultimately to a final response.

Current project is a detailed investigation into the cellular and molecular action of the acid labile subunit (ALS) that is one of the insulin like-growth factor I (IGF-I) binding proteins in the circulation system, and growth hormone receptor (GHR) signaling pathway. In postnatal life, IGF-I and -II circulate as 150 kDa ternary complexes consisting of one molecule each of IGFBP-3 or IGFBP-5, IGF-I or IGF-II and ALS. Incorporation of IGFs in ternary complexes extends their half-lives from 10 min (free IGF) or 30 min (IGF in binary complexes) to over 15 h. ALS knock-out mice showed a reduction in circulating IGF-I (62%) and IGFBP-3 (88%). The synthesis of IGF-I and IGFBP-3 in liver and kidney remains unaltered, indicating that absence of ALS caused increasing turnover of IGF-I and IGFBP-3. ALS knock-out mice suffered at 13% growth retardation. ALS is also synthesized predominantly in liver by GH-mediated signal transduction through GH-responsive element, called ALSGAS1 between nt -633 and nt -625 of the mouse ALS promoter. This element is shown to bind STAT5 in a GH dependent manner and to mediate the effect of GH on ALS gene transcription. One of mechanisms involved in the termination of GH signaling is the dephosphorylation of critical tyrosine residues in the activated GHR-JAK2 complex. Protein tyrosine phosphatase-1B (PTP-1B) associates with JAK2 in a GH-dependent manner and dephosphorylates the tandemly arranged tyrosine residues responsible for JAK2 activation. Over-expression PTP-1B in H4-II-E cells blunts STAT5-mediated gene transcription in response to GH, suggesting that PTP-1B is one of the phosphatases capable of terminating GH signaling.