PubMed Journals: J Biol Chem

  Source:		PMID: 8663493

    		J Biol Chem. 1996 Jul 26;271(30):18217-23.
			Involvement of p90rsk in neurite outgrowth
			mediated by the cell adhesion molecule L1.

			Wong EV(1), Schaefer AW, Landreth G, Lemmon

			Author Information
			(1) Department of Neurosciences,
			Case Western Reserve University, Cleveland,
			Ohio 44106-4975, USA.

			L1 is a neural cell adhesion molecule that
			has been shown to help guide nascent axons
			to their targets. This guidance is based
			on specific interactions of L1 with its
			binding partners and is likely to involve
			signaling cascades that alter cytoskeletal
			elements in response to these binding events.
			We have examined the phosphorylation of
			L1 and the role it may have in L1-directed
			neurite outgrowth. Cytosolic extracts from
			nerve growth factor-stimulated PC12 cells
			were fractionated by anion-exchange chromatography,
			and an activity was found that phosphorylated
			the cytoplasmic domain of L1. This activity
			was then assayed using a battery of L1-derived
			synthetic peptides. Based on these peptide
			assays and sequencing of radiolabeled L1
			proteolytic fragments, the phosphorylation
			site was determined to be Ser1152. Western
			blot analysis demonstrated that the L1 kinase
			activity from PC12 cells that phosphorylated
			this site was co-eluted with the S6 kinase,
			p90(rsk). Moreover, S6 kinase activity and
			p90(rsk) immunoreactivity co-immunoprecipitate
			with L1 from brain, and metabolic labeling
			studies have demonstrated that Ser1152 is
			phosphorylated in vivo in the developing
			rat brain. The phosphorylation site is located
			in a region of high conservation between
			mammalian L1 sequences as well as L1-related
			molecules in vertebrates from fish to birds.
			We performed studies to investigate the
			functional significance of this phosphorylation.
			Neurons were loaded with peptides that encompass
			the phosphorylation site, as well as the
			flanking regions, and their effects on neurite
			outgrowth were observed. The peptides, which
			include Ser1152, inhibit neurite outgrowth
			on L1 but not on a control substrate, laminin.
			A nonphosphorylatable peptide carrying a
			Ser to Ala mutation did not affect neurite
			outgrowth on either substrate. These data
			demonstrate that the membrane-proximal 15
			amino acids of the cytoplasmic domain of
			L1 are important for neurite outgrowth on
			L1, and the interactions it mediates may
			be regulated by phosphorylation of Ser1152.

			PMID: 8663493 [Indexed for MEDLINE]

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