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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 22

Module 2: Figure Rho-regulated kinases

Rac Cdc42 LIMK1/2
GTP GTP
MLCK
PBD Kinase
P21-activated kinase (PAK)
Kinase PBD

Cdc42
MYPT1 GTP
CRD
Myotonic dystrophy Kinase CC1 CC2 3 PH CH PBD
kinase-related Cdc42-binding
kinase (MRCK) Kinase CC1 CC2 3 PH CH PBD

LIMK1/2 Rho
FilGAP GTP
CRD
Kinase CC PBD PH
Rho kinase (ROK)
Kinase CC PBD PH

Structure of Rho GTPase-regulated kinases.
The Rho family exert many of their actions by stimulating protein kinases such as PAK, MRCK and ROK. These kinases exist as homodimers with
PAK being arranged in a head-to-tail manner, whereas MRCK and ROK have a parallel alignment. The GTP-bound form of these p21 monomeric
G proteins bind to a p21-binding domain (PBD). CC, coiled-coil domain: CH, citron homology domain; CRD, cysteine-rich domain; FilGap, filamin
GTPase-activating protein; MLCK, myosin light chain kinase; PH, pleckstrin homology domain.

Module 2: Figure basic Ca 2 + signalling mechanism

STIMULUS
Time
domain

Exocytosis s

Contraction ms
ON REACTIONS
2+ Ca 2+ Metabolism sec
Ca Gene
100 nM OFF REACTIONS 500nM transcription min
Fertilization
Proliferation hr
Hypertrophy

The basic mechanism of Ca 2 + signalling.
The concentration of Ca 2 + in cells at rest is approximately 100 nM, but this increases to 500 nM or more following a stimulus that activates the Ca 2 +
ON reactions. When the stimulus is removed, the Ca 2 + OFF reactions return the concentration of Ca 2 + to its resting level. Ca 2 + is a universal signal
capable of activating many different cellular processes operating over a very wide time domain.

chain kinase (MLCK), myosin can begin to interact with phatase targeting subunit 1 (MYPT1) (Module 5: Table PP1
actin to induce contraction. ROK can influence the phos- regulatory, targeting and inhibitory subunits).
phorylation of MLC by inhibiting the protein phosphatase ROK may also function to inhibit endocytosis by phos-
1 by phosphorylating the scaffolding protein myosin phos- phorylating endophilin.

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