Characterization of Additional Casein Kinase I Sites in the C‐Terminal “Tail” Region of Chicken and Rat Neurofilament‐M

Shaw, Gerry; Miller, Rehae; Wang, Dengshun; Tang, Dali; Hollander, Brian A.; Bennett, Gudrun S.

doi:10.1046/j.1471-4159.1997.69041729.x

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…We next compared the influence of overexpression of GSK3b and CK1, because the majority of NF-H consensus sites for these kinases exist within the distal-most 187 amino acids (Chen et al, 2000;Hollander and Bennett, 1992;Hollander et al, 1996;Sasaki et al, 2002;Shaw et al, 1997), on bundling of GFP-NF-H and GFP-NF-HD187 (Fig. 8E).…”

Section: Ck1 Inhibits Neurofilament Phosphorylation Within Perikarya mentioning

confidence: 99%

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Lee

Pant²,

Shea

2014

Journal of Cell Science

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C-terminal neurofilament phosphorylation mediates cation-dependent self-association leading to neurofilament incorporation into the stationary axonal cytoskeleton. Multiple kinases phosphorylate the C-terminal domains of the heavy neurofilament subunit (NF-H), including cyclin-dependent protein kinase 5 (CDK5), mitogenactivated protein kinases (MAPKs), casein kinase 1 and 2 (CK1 and CK2) and glycogen synthase kinase 3b (GSK3b). The respective contributions of these kinases have been confounded because they phosphorylate multiple substrates in addition to neurofilaments and display extensive interaction. Herein, differentiated NB2a/d1 cells were transfected with constructs expressing GFP-tagged NF-H, isolated NF-H sidearms and NF-H lacking the distal-most 187 amino acids. Cultures were treated with roscovitine, PD98059, Li + , D4476, tetrabromobenzotriazole and calyculin, which are active against CDK5, MKK1 (also known as MAP2K1), GSK3b, CK1, CK2 and protein phosphatase 1 (PP1), respectively. Sequential phosphorylation by CDK5 and GSK3b mediated the neurofilamentneurofilament associations. The MAPK pathway (i.e. MKK1 to ERK1/ 2) was found to downregulate GSK3b, and CK1 activated PP1, both of which promoted axonal transport and restricted neurofilamentneurofilament associations to axonal neurites. The MAPK pathway and CDK5, but not CK1 and GSK3b, inhibited neurofilament proteolysis. These findings indicate that phosphorylation of neurofilaments by the proline-directed MAPK pathway and CDK5 counterbalance the impact of phosphorylation of neurofilaments by the non-proline-directed CK1 and GSK3b.

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Section: Ck1 Inhibits Neurofilament Phosphorylation Within Perikarya mentioning

confidence: 99%

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Lee

Pant²,

Shea

2014

Journal of Cell Science

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“…Ser473 in the NF‐L E‐segment is phosphorylated in vivo (Xu et al, 1990) by casein kinase II (Nakamura et al, 1999). The chicken NF‐M E‐segment is phosphorylated by NF‐associated casein kinase I (Hollander and Bennett, 1992; Hollander et al, 1996; Shaw et al, 1997). We have shown that Ser493 in the NF‐H E‐segment is phosphorylated by glycogen synthase kinase 3β (GSK3β) in vitro and invivo (Sasaki et al, 2002).…”

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Novel axonal distribution of neurofilament‐H phosphorylated at the glycogen synthase kinase 3β‐phosphorylation site in its E‐segment

Sasaki

Ishiguro

Hisanaga

2009

J of Neuroscience Research

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The Ser493 residue in the E-segment of the rat neurofilament heavy chain (NF-H) is phosphorylated by glycogen synthase kinase 3beta (GSK3 beta) in vitro and in spinal cord. We examined Ser493 phosphorylation by analyzing developmental changes and cellular distribution of phospho-Ser493 using phosphorylation-site-specific antibodies. This residue was phosphorylated in NF-H prepared from human, rat, and mouse spinal cord, all species in which the amino acid sequence of NF-H is known. Phosphorylated Ser493 appeared on postnatal day 2 in rat brain, at the same time when NF-H is first detected. It gradually increased together with the increase in total NF-H during brain development. Phospho-Ser493 was detected on the phosphorylated form of NF-H at multiple Lys-Ser-Pro (KSP) repeats, which are distributed mainly in axons. In rat ventral horn, phosphorylated Ser493 was localized in axons but not in cell bodies or dendrites. However, the distributions of phosphorylated Ser493 and KSP phosphorylation in axons were not identical. Ser493 was continuously phosphorylated at nodes of Ranvier, whereas the KSP sites were dephosphorylated. Ser493 was also phosphorylated in unmyelinated regions of optic nerve axons. A biochemical difference in phosphorylation between Ser493 and KSP repeats was also found; the subtle phosphorylation at Ser493 was detected in NF-H unphosphorylated at the KSP repeats by immunoblotting cerebral cortex extracts. These results indicate that Ser493 in the NF-H E-segment is a novel site that is phosphorylated in both the myelinated and the unmyelinated regions of axons.

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“…We have identified five such sites in the acidic amino‐terminal portion of the chicken NF‐M tail that are also phosphorylated in vivo (Ser 464 , Ser 471 , Ser 502 , Ser 528 , and Ser 536 ; Fig. 1A) (Hollander et al, 1996 ; Shaw et al, 1997). At least three of these are conserved in the corresponding mammalian sequences (Shaw et al, 1997).…”

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confidence: 99%

“…1A) (Hollander et al, 1996 ; Shaw et al, 1997). At least three of these are conserved in the corresponding mammalian sequences (Shaw et al, 1997). These sites all share a casein kinase I (CKI) consensus motif (D/E 2‐4 X 0‐2 XS/T), and they can be phosphorylated in vitro by pure CKI (Hollander et al, 1996 ; Shaw et al, 1997).…”

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confidence: 99%

“…At least three of these are conserved in the corresponding mammalian sequences (Shaw et al, 1997). These sites all share a casein kinase I (CKI) consensus motif (D/E 2‐4 X 0‐2 XS/T), and they can be phosphorylated in vitro by pure CKI (Hollander et al, 1996 ; Shaw et al, 1997). The finding that CKI‐like activity is associated with isolated NFs (Link et al, 1993 ; Hollander et al, 1996) is consistent with the participation of CKI in the phosphorylation of NF‐M in vivo, although the functional significance is currently not known.…”

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confidence: 99%

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Relationship Between Casein Kinase I Isoforms and a Neurofilament‐Associated Kinase

Green²,

Bennett³

1999

Journal of Neurochemistry

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Purified neurofilaments (NFs) contain an associated kinase (NFAK) activity that phosphorylates selectively a subset of sites in the tail of NF-M and has properties consistent with casein kinase I (CKI). Because CKI consists of a family of as many as seven genes (␣, ␤, ␥1-3, ␦, and ⑀), we investigated the extent to which different CKI isoforms contribute to NFAK activity. Using an NF-M-derived substrate, we determined that NFAK activity copurified with casein kinase activity through two purification steps. In an in-gel kinase assay, NFAK activity occurred at 36 -40 kDa, corresponding to the size of CKI␣ isoforms. Chicken neurons express transcripts encoding four alternatively spliced variants of CKI␣ (CKI␣, CKI␣S, CKI␣L, and CKI␣LS) differing in the presence or absence of two inserts, L and S. Using antibodies against different isoforms or with broad CKI specificity, we determined that all four CKI␣ variants, as well as other CKI family members, are present in chicken brain. However, only CKI␣ and CKI␣S could be detected in purified NFAK. Also, immunoprecipitation studies showed that CKI␣ and CKI␣S together account for NFAK activity. These findings raise the possibility that only a subset of CKI isoforms may be able to associate with and/or phosphorylate NFs.

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Characterization of Additional Casein Kinase I Sites in the C‐Terminal “Tail” Region of Chicken and Rat Neurofilament‐M

Cited by 14 publications

References 31 publications

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Novel axonal distribution of neurofilament‐H phosphorylated at the glycogen synthase kinase 3β‐phosphorylation site in its E‐segment

Relationship Between Casein Kinase I Isoforms and a Neurofilament‐Associated Kinase

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