High impact information on Camk1

• Activity-dependent dendritic outgrowth and branching in cultured hippocampal neurons and slices is mediated through activation by CaM-dependent protein kinase kinase (CaMKK) of the membrane-associated gamma isoform of CaMKI [1].
• These proteins were unphosphorylated and were bound only to the Thr177-phosphorylated CaM-KI catalytic domain [2].
• Unlike wild-type CaM-KI, however, phosphorylation of Thr177 in the chimera mutants by CaM-KK resulted in generation of significant autonomous activities, indicating that the phosphorylation of Thr in the activation loop is sufficient to partially release the autoinhibitory region of CaM-KIV from the catalytic core [3].
• We have shown that the kinetics of Thr196 phosphorylation of CaM-KIV by CaM-KK is well correlated with the generation of its autonomous activity, although Thr177 phosphorylation of CaM-KI does not induce its autonomous activity [3].
• In situ hybridization analysis has demonstrated that CaMKI gamma mRNA is expressed in a distinct pattern from other isoforms of CaMKI with predominant expression in some restricted brain regions such as the olfactory bulb, hippocampal pyramidal cell layer of CA3, central amygdaloid nuclei, ventromedial hypothalamic nucleus and pineal gland [4].

Biological context of Camk1

• Translocation of CaMKI-alpha into the nucleus involves a conserved sequence located within the catalytic core [5].
• We report that cytoplasmic localization of CaMKI-alpha depends on CRM1-mediated nuclear export mediated through a Rev-like nuclear export signal in the CaMKI-alpha regulatory domain [5].
• Treatment of neurons with 1,8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), an inhibitor of CaMKK, causes a similar change in morphology and reduction in growth cone motility, and this inhibition can be rescued by transfection with an STO-609-insensitive mutant of CaMKK or by transfection with constitutively active CaMKI [6].
• This is the first demonstration that the activation of the CaM-KI cascade induces myosin II phosphorylation, resulting in regulation of actin filament organization in mammalian cells [7].
• These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction [8].

Anatomical context of Camk1

• CaMKI is found throughout the cell cytosol, including the growth cone [6].
• Growth cones of neurons expressing dnCaMI or dnCaMKK, the upstream activator of CaMKI, exhibit collapsed morphology with a prominent reduction in lamellipodia [6].
• Furthermore, a kinase-negative form of CaM-KI (CaM-KI(1-293,K49E)) significantly reduced reorganization of actin filaments, indicating a dominant negative effect [7].
• Transient expression of the Ca(2+)/CaM-independent form of CaM-KI (CaM-KI(1-293)) in HeLa cells induced Ser-19 phosphorylation of myosin, II accompanied by reorganization of actin filaments in the peripheral region of the cells [7].

Enzymatic interactions of Camk1

• We recently cloned a calmodulin-dependent protein kinase kinase (CaM-KK) which phosphorylates and activates CaM-KI and CaM-KIV [Tokumitsu, H., Enslen, H., and Soderling, T. R. (1995) J. Biol. Chem. 270, 19320-19324] [9].

Regulatory relationships of Camk1

• Interaction of CaMKI-alpha with a CRM1 complex in vitro is enhanced by incubation with calcium/calmodulin [5].

Other interactions of Camk1

• These results identify CaMKI as a positive transducer of growth cone motility and axon outgrowth and provide a new physiological role for the CaMKK-CaMKI pathway [6].
• Calcium/calmodulin-dependent protein kinase I-alpha (CaMKI-alpha) is a ubiquitous cytosolic enzyme that phosphorylates a number of nuclear proteins in vitro and has been implicated in transcriptional regulation [5].
• Here, we have isolated and determined the complete primary structures of two alternatively splicing isoforms of CaMKI termed CaMKI gamma 1 and -gamma 2 [4].
• Ca2+/calmodulin-dependent protein kinase I (CaMKI), originally identified as a protein kinase phosphorylating synapsin I, has been shown to constitute a family of closely related isoforms (alpha, beta and gamma) [4].
• Transfection experiments using expression plasmids for constitutively active forms of CaMKI, CaMKII, or CaMKIV show that CaMKII is the most effective activator of prolactin promoter expression [10].

Analytical, diagnostic and therapeutic context of Camk1

• To search for the substrates of Ca2+/calmodulin-dependent protein kinase I (CaM-KI), we performed affinity chromatography purification using either the unphosphorylated or phosphorylated (at Thr177) GST-fused CaM-KI catalytic domain (residues 1-293, K49E) as the affinity ligand [2].

References