2013年7月8日，清华大学生命科学学院潘俊敏教授研究组在《美国科学院院刊》（PNAS）上在线发表了题为“Activation loop phosphorylation of a protein kinase is a molecular marker of organelle size that dynamically reports flagellar length”的研究论文，报道了蛋白激酶CALK在纤毛长度调控体系中的作用，该工作证实细胞存在纤毛长度感知系统，实现自身纤毛长度的主动调控。
纤毛是真核生物一种保守的细胞器官，纤毛的缺陷会造成众多的人类疾病和发育异常。因此研究纤毛长度调控不仅可以解答细胞器大小调控这一基本的生物学问题，还可以为纤毛相关疾病的研究提供新的线索。纤毛长度调控理论目前还存在很大的争论，主要争议点为纤毛长度调控是细胞的主动行为还是被动行为。
该工作发现CALK激酶活性调控关键位点T193磷酸化和纤毛长度之间有密切关系，在纤毛组装和解聚两个过程中，T193位点磷酸化修饰比例都随着纤毛长度发生线性变化。进一步的研究发现纤毛长度突变体和环境诱导的纤毛长度异常的野生型细胞也有类似现象。该研究证实细胞存在纤毛长度感知体系实时感受纤毛长度，并可以将纤毛长度信号转化为蛋白质磷酸化修饰信号，反馈调控纤毛长度。该工作对于细胞器大小调控具有普遍意义，说明细胞很可能广泛的存在细胞器主动感知系统，并主动调控其自身细胞器体积来适应细胞要求。
这是潘俊敏教授研究组继2011年在《Current Biology》上发表纤毛长度调控研究后的又一重大发现，为细胞器大小调控理论提供了新的理论。该工作是由博士生曹木青同学为主，并与美国西南医学中心共同合作完成。（生物谷Bioon.com）
doi:10.1073/pnas.1302364110
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Activation loop phosphorylation of a protein kinase is a molecular marker of organelle size that dynamically reports flagellar length
Muqing Caoa, Dan Menga, Liang Wanga, Shuqing Beib, William J. Snellc,1, and Junmin Pana,1
Specification of organelle size is crucial for cell function, yet we know little about the molecular mechanisms that report and regulate organelle growth and steady-state dimensions. The biflagellated green alga Chlamydomonas requires continuous-length feedback to integrate the multiple events that support flagellar assembly and disassembly and at the same time maintain the sensory and motility functions of the organelle. Although several length mutants have been characterized, the requisite molecular reporter of length has not been identified. Previously, we showed that depletion of Chlamydomonas aurora-like protein kinase CALK inhibited flagellar disassembly and that a gel-shift–associated phosphorylation of CALK marked half-length flagella during flagellar assembly. Here, we show that phosphorylation of CALK on T193, a consensus phosphorylation site on the activation loop required for kinase activity, is distinct from the gel-shift–associated phosphorylation and is triggered when flagellar shortening is induced, thereby implicating CALK protein kinase activity in the shortening arm of length control. Moreover, CALK phosphorylation on T193 is dynamically related to flagellar length. It is reduced in cells with short flagella, elevated in the long flagella mutant, lf4, and dynamically tracks length during both flagellar assembly and flagellar disassembly in WT, but not in lf4. Thus, phosphorylation of CALK in its activation loop is implicated in the disassembly arm of a length feedback mechanism and is a continuous and dynamic molecular marker of flagellar length during both assembly and disassembly.
