PubMed Journals: J Biol Chem

  Source:		PMID: 10559204

    		J Biol Chem. 1999 Nov 19;274(47):33287-95.
			Human JIK, a novel member of the STE20 kinase
			family that inhibits JNK and is negatively
			regulated by epidermal growth factor.

			Tassi E(1), Biesova Z, Di Fiore PP, Gutkind
			JS, Wong WT.

			Author Information
			(1) Oral and Pharyngeal Cancer Branch, NIDCR,
			National Institutes of Health, Bethesda,
			Maryland 20892-4330, USA.

			Mammalian members related to Saccharomyces
			cerevisiae serine/threonine kinase STE20
			can be divided into two subfamilies based
			on their structure and function. The PAK
			subfamily is characterized by an N-terminal p21-binding
			domain (also known as CRIB domain), a C-terminal
			kinase domain, and is regulated by the small
			GTP-binding proteins Rac1 and Cdc42Hs. The
			second group is represented by the GCK-like members,
			which contain an N-terminal catalytic domain
			and lack the p21-binding domain. Some of
			them have been demonstrated to induce c-Jun
			N-terminal kinase/stress-activated protein
			kinase (JNK/SAPK) cascade, while others
			have been shown to be activated by a subset
			of stress conditions or apoptotic agents,
			although little is known about their specific
			function. Here, we have identified a novel
			human STE20-related serine/threonine kinase,
			belonging to the GCK-like subfamily. This
			kinase does not induce the JNK/SAPK pathway,
			but, instead, inhibits the basal activity
			of JNK/SAPK, and diminishes its activation
			in response to human epidermal growth factor
			(EGF). Therefore, we designated this molecule
			JIK for JNK/SAPK-inhibitory kinase. The
			inhibition of JNK/SAPK signaling pathway
			by JIK was found to occur between the EGF
			receptor and the small GTP-binding proteins
			Rac1 and Cdc42Hs. In contrast, JIK does
			not activate nor does it inhibit ERK2, ERK6,
			p38, or ERK5. Furthermore, JIK kinase activity
			is not modulated by any exogenous stimuli,
			but, interestingly, it is dramatically decreased
			upon EGF receptor activation. Thus, JIK
			might represent the first member of the
			STE20 kinase family whose activity can be
			negatively regulated by tyrosine kinase
			receptors, and whose downstream targets
			inhibit, rather than enhance, JNK/SAPK activation.

			PMID: 10559204 [Indexed for MEDLINE]

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