Cellular Basis Of Action Of Gastrointestinal Peptides/Growth factors

在这一年中，我们写了一些邀请审查和批判性分析，其中部分是基于我们的研究的细胞基础上的行动，各种胃肠道肽（蛙皮素受体家族，VIP-PACAP肽家族，内皮素受体家族，神经降压素。其中包括报告了通过EGF受体家族的反式激活这些受体中的一些对癌症生长的影响的论文，以及PACAP/VIP和蛙皮素受体家族分别在各种人类疾病和CNS癌症中的可能治疗作用的综述。 最近的研究表明，在正常和肿瘤组织中，胃肠激素（GI）和GI生长因子（GF）可通过刺激多个细胞内酪氨酸/丝氨酸/苏氨酸磷酸化（TyrP）信号级联以及通过生长因子受体的反式激活来引起细胞生长。然而，目前对许多胃肠激素/生长因子激活这些级联的能力知之甚少。在今年的一项研究中，我们报告了肺癌细胞中的神经肽PACAP刺激这些肿瘤的生长，同时主要通过一些EGFR家族成员（包括EGFR，HER 2和HER 3）的反式激活来进行信号传导。在这些细胞中，PACAP刺激EGFR/HER 3和HER 2/HER 3二聚体的形成，导致增殖。最近的研究，包括我们的研究表明，在不同的细胞中，这些肽刺激酪氨酸磷酸化和受体酪氨酸激酶的能力的机制涉及许多不同的机制，这是详细审查PACAP-VIP，蛙皮素，内皮素和神经降压素在今年的邀请审查。这些GPCR激活这些酪氨酸激酶级联的新能力证明了这些受体在许多生理/病理过程中的重要性，特别是正常和癌症组织的生长级联，开辟了新的治疗方法。

During the year we have written a number of invited reviews and critical analyses which are partially based on our studies of the cellular basis of action of various gastrointestinal peptides (bombesin receptor family, VIP-PACAP peptide family, endothelin receptor family, neurotensin. These include papers reporting the effects of activation of a number of these receptors on cancer growth through the transactivation of the EGF receptor family as well as reviews of the possible therapeutic roles of PACAP/VIP and bombesin receptor families in various human diseases and CNS cancers, respectively. Recent studies show that in both normal and neoplastic tissues, gastrointestinal hormones (GI) and GI growth factors (GF) may cause cell growth by stimulating multiple intracellular tyrosine/serine/threonine phosphorylation (TyrP) signaling cascades as well as by transactivation of growth factor receptors. However, at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades. In a study this year we report that the neuropeptide, PACAP in lung cancer cells stimulates growth of these tumors while signaling principally by transactivation of a number of EGFR family members including EGFR, HER2 and HER3. In these cells PACAP stimulated the formation of EGFR/HER3 and HER2/HER3 dimers resulting in proliferation. Recent studies, including ours have demonstrated that in different cells the mechanisms of the ability of these peptides to stimulate tyrosine phosphorylation and receptor tyrosine kinases involves a number of different mechanisms, and this was reviewed in detail for PACAP-VIP, Bombesin, endothelin and neurotensin in an invited review this year. The novel abilities of these GPCRs to activate these tyrosine kinase cascades are demonstrating the importance of these receptors in numerous physiological/pathological processes, particular growth cascades of both normal and cancer tissues, opening new therapeutic approaches.