*nlm.life
			PubMed Journals: Eur J Biochem

  Source:		PMID: 11422372


    		Eur J Biochem. 2001 Jun;268(12):3423-31.
     
			Proteolytic processing of a human salivary
			proline-rich protein precursor by proprotein
			convertases.

			Chan M(1), Bennick A.

			Author Information
			(1) Department of Biochemistry,
			University of Toronto, Toronto, Canada.

			Salivary proline-rich proteins (PRPs) are
			synthesized as precursors that are cleaved
			before secretion giving rise to glycosylated
			PRPs which have lubricating function and
			basic PRPs which are potent precipitators
			of dietary tannins. The putative cleavage
			sites in the precursors for basic and glycosylated
			PRPs all conform to the sequence RSXR downward
			arrowS (X can be A, S or P) in agreement
			with the recognition sequence (RXXR downward
			arrow) for various proprotein convertases.
			PRB4S, a proprotein giving rise to a basic
			PRP (IB-5) as well as a glycosylated PRP
			(II-1) was synthesized by in vitro
			transcription-translation. It was cleaved
			by furin at RSAR downward arrowS(173-178)
			giving rise to two proteins II-1 and IB-5.
			Similarly another precursor with the sequence
			RSAR downward arrowS(173-178) was also cleaved
			by furin. This together with previous results
			show that in vitro furin can cleave all
			RSXR downward arrowS sequences in the proproteins
			that give rise to glycosylated and basic
			PRPs. To demonstrate cellular cleavage,
			a human submandibular cell line (HSG) was
			transfected with a vector encoding PRB4S.
			This resulted in secretion of II-1 and IB-5.
			The degree of cleavage was enhanced by coexpressing
			furin and PRB4S. No cleavage occurred if
			the cells expressed a mutant PRB4S, R177Q,
			where the furin cleavage site had been destroyed.
			Cleavage was also inhibited if a furin inhibitor
			was coexpressed with PRB4S. Incubating the
			cells at 20 degrees C which blocks exit
			of proteins from the trans-Golgi network
			demonstrated that cleavage occurs before
			exit of the proteins from this network.
			These results show that furin may be responsible
			for in vivo cleavage of PRP precursors.
			Transfecting furin-deficient RPE.40 cells with
			a vector encoding PRB4S also led to secretion
			of II-1 and IB-5 showing that convertases
			other than furin can also cleave PRB4S in
			tissue culture.

			PMID: 11422372 [Indexed for MEDLINE]

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