复旦大学上海医学院马兰教授最近在PNAS上发表研究新进展Kinase activity-independent regulation of cyclin pathway by GRK2 is essential for zebrafish early development。
G蛋白偶联受体（G Protein-coupled receptor，GPCR）激酶（GRKs）属丝氨酸/酪氨酸. 蛋白激酶家族，其亚型广泛存在于各种组织，能特异地使活化的G蛋白偶联受体(GPCR)发生磷酸化及脱敏化, 从而终止后者介导的信号转导通路.
在本研究中，马兰教授等人主要解析GRKs在斑马鱼的胚胎发育过程中的作用。这项研究结果表明，在斑马鱼胚胎的早期发育过程中，GRK2的调节起十分重要的作用。详细的解析了GRK2对斑马鱼胚胎发育的调节机制。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS June 5, 2009, doi: 10.1073/pnas.0812105106
Kinase activity-independent regulation of cyclin pathway by GRK2 is essential for zebrafish early development
Xi Jiang, Peng Yang and Lan Ma,1
1 State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China
Abstract
G protein-coupled receptor (GPCR) kinases (GRKs) are known as a family of serine/threonine kinases that function as key regulators of GPCRs, as well as other types of receptors. Extensive studies of GRKs at the cellular and organismal levels have led to a consensus that GRK-catalyzed phosphorylation of receptors is the primary mechanism underlying their physiological functions. Here, we report that down-regulation of GRK2 in zebrafish embryos with GRK2 morpholino results in developmental early arrest and, interestingly, that this arrest can be rescued by exogenous expression of a GRK2 kinase-dead mutant, K220R. A physical interaction between GRK2 and cyclin B1 regulator patched homolog 1 (PTCH1), stimulated by Hedgehog (Hh), rather than GRK2-mediated phosphorylation of downstream targets, appears as the underlying mechanism. We identify residues 262–379 as the PTCH1-binding region (BP). Interaction of GRK2, K220R, and BP with PTCH1 reduces the association of PTCH1 with cyclin B1 and disrupts PTCH1-mediated inhibition of cyclin B1 nuclear translocation, whereas the PTCH1-binding deficient GRK2 mutant (Δ312–379) does not. Cell cycle and cell proliferation assays show that overexpressing PTCH1 remarkably inhibited cell growth and this effect could be attenuated by GRK2, K220R, or BP, but not Δ312–379. In vivo studies show that BP, as well as the nuclear-localizing cyclin B1 mutant, is effective in rescuing the early arrest phenotype in GRK2 knockdown embryos, but Δ312–379 is not. Our data thus reveal a novel kinase activity-independent function for GRK and establish a role for GRK2 as a cell-cycle regulator during early embryonic development.
