Biochemistry Online: An Approach Based on Chemical Logic

CHAPTER 9 - SIGNAL TRANSDUCTION

C: SIGNALING PROTEINS

BIOCHEMISTRY - DR. JAKUBOWSKI

04/16/16

Learning Goals/Objectives for Chapter 9C:
After class and this reading, students will be able to

define kinases and phosphatases and their role in signal transduction
define primary and secondary messengers and give specific examples of each
describe the role of G proteins in coupling ligand induced conformational changes in the bound receptor to activation of specific effector proteins such as adenylate cyclase and phospholipase
differentiate between kinases activated by second messengers and those activated by primary messengers (ligand-gated receptor Tyr kinases)
describe the structural characteristics of G protein coupled serpentine receptors and ligand gated receptor tyrosine kinases
draw a diagram showing the general features of kinases mediated signal transduction pathways that lead to activation of gene expression
differentiate between neuron responses mediated by neurotransmitters on binding gated receptor/ion channels compares to G-protein coupled receptors

Estonian Translation √ by Anna Galovich

C8. Mitogen Activated Protein Kinases

It is often the case that occupied receptors activate protein kinases, which activate other protein kinases, which activate yet other protein kinases to produce phospho-proteins which may act as transcription factors. An example is the mitogen activated protein kinase (MAPK system). A mitogen is an external chemical signal that causes mitosis or cell division. Activated of transcription factors by their phosphorylation through a mitogen activated kinase is required. The sequence of events is:

binding of external signal to membrane receptor and activation of receptor kinase
phosphorylation of receptor kinase and interaction with an activator GTP binding protein like ras
binding of activated G-protein to and activation of a mitogen activated protein kinase kinase kinase (MAPKKK)
MKKK phosphorylates and activates another kinase, MAPKK
MKK phosphorylates and activates mitogen activated protein kinase, MAPK
MAPK phosphorylates inactive transcription factors (or other proteins) and activates them. Unfortunately (from a naming point of view) when the activated proteins are themselves protein kinase, they are called mitogen activated protein kinase activated protein kinases (MAPKAPK)

There are seven types of MAPKs, four conventional and three atypical. Four typical ones are described in the table below.

Activator GTP binding protein	Ras:GTP
MAPKKK or MAPK3	Raf-1A/B c-Mos	MEKK1-4 DLK MLK2	MEKK1-4 DLK MLK2	MEKK2/3 Tpl-2
MAPKK or MAPK2	MEK1,2	MEK4,7	MEK3,6	MEK5
MAPK or MAK	ERK1,2	JNK1-3	p38	ERK5
MAPKAPK	RSK 1-4 MNK2 MSK 1,2	MK2,3	MSK1,2 MK2,3	RSK1-4
An eventual Protein Target	c-Jun	c-Jun

MAP Kinase System from Cell Signaling

MAP Kinase System animation from Promega

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